Changes In Contractile Activity Research Articles

Транскрипционные факторы в скелетной мышце человека, ассоциированные с однократным и регулярными силовыми упражнениями

Skeletal muscle plasticity is the ability to change morphofunctional properties in response to changes in contractile activity. Strength training increases the size of muscle fibers and maximum strength with the activation of protein synthesis. Regulation of these changes at the gene level has not been investigated properly. This study aimed to identify transcription factors associated with changes in the transcriptome of the human skeletal muscle in the context of single and regular strength exercises. We assessed changes in the transcriptomic profile of m. vastus lateralis of 10 young men (mean age 23 (20.8 - 25.9) years) before and after 12-week leg extensor muscles strength training course, as well as before, 8 and 24 hours after a single exercise. Transcriptomic profiling involved RNA sequencing, search for binding motifs and the associated transcription factors. Bioinformatic methods of statistics, FastQC, GraphPad Prizm 8, DAVID, R enabled analysis of the data acquired. The strength training course resulted in the enrichment of the functional groups of genes "secreted proteins", "extracellular matrix" and "basal membrane" (p < 0.05). Transcriptomic responses and the associated transcription factors differed 8 and 24 hours after a single session as well as after regular training sessions. Transcription factors involved in adjustment to regular and one-time loads participate in myogenesis, angiogenesis, regulation of fiber phenotype, proteostasis and other processes. Thus, regulation of gene expression during adjustment to the resistance training loads is a complex process that involves many transcription factors with different functions. Investigation of the role played by these factors in the context of adjustment to exercising is a potentially rewarding task.

Tissue regeneration and gut microbiota-skeletal muscle axis via microRNAs and nutrition: a systematic review

Introduction: In the scenario of muscle regeneration in athletes, maintenance of skeletal muscle function is the prerequisite for tissue homeostasis and increased performance. MicroRNAs play a positive role in expanding our understanding of the controlling factors for skeletal muscle function. Recent progress has been made regarding gut microbiota, regenerative nutrition, and skeletal muscle metabolism. Objective: It was to carry out a systematic review of the main relations of regeneration of skeletal muscle-gut microbiota through nutrological functions, cells, and microRNAs. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from February to April 2023 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 217 articles were found. A total of 97 articles were fully evaluated and 49 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 54 studies at high risk of bias and 34 studies that did not meet the GRADE. It was concluded that miRNAs are widely present in skeletal muscle and play an irreplaceable tuning role in the proliferation, differentiation, apoptosis, development, and other physiological processes of skeletal muscle cells. The proposal that miRNAs are primarily involved in the cell's stress response makes miRNAs ideal for mediating the skeletal muscle response to changes in contractile activity. Research has accumulated evidence that confirms that miRNAs have played an important regulatory role in cell proliferation and differentiation, thus regulating skeletal muscle growth as highlighted in the small intestine by intestinal stem cells (LGR5+). The ketogenic or high-glucose diet regulates the self-renewal balance of LGR5+. Self-renewal and HSC differentiation can be regulated by manipulating vitamin C, A, or D levels and valine restriction. The composition of each athlete's microbiome influences sports performance.

Capsaicin fails to produce changes in contractile tension in large gut of neonate rats

Objectives: Capsaicin, the most pungent constituent of chilli pepper (Capsicum annuum L.), is known to alter the physiological activity of the gut. Capsaicin mediates its action through a transient receptor potential vanilloid type 1 (TRPV1) channel. The action of capsaicin on gut smooth muscle varies from segment to segment in different species. The earlier studies were carried out in adult animals only, and its status in the neonate gut, which is in a development stage, is not known. Objective: Therefore, the present study was done to assess the effect of capsaicin on the large gut of neonates. Materials and Methods: In an organ bath preparation, isometric contractions were recorded from segments of dissected rat colon and rectum. The gut segments were exposed to cumulative concentrations of capsaicin (0.01 nM–3 µM) and a capsaicin-induced contractile response was observed. TRPV1 receptor antagonist capsazepine (1 µM) and a nitric oxide synthase inhibitor, L-NAME (100 µM), were used to assess their blocking effect on capsaicin-induced contractile response. Results: Capsaicin raised contractile tension in the colon and rectum of adult rats but not in neonate rats. In adult rats, capsazepine pre-treatment (1 µM) failed to block the capsaicin-induced response in the colon, but in the lower concentrations, it increased contractile tension in the rectum. Pre-application of L-NAME (100 µM) potentiated capsaicin-induced response in the adult rectum and neonate’s colon but had no effect in the neonate rectum and adult colon. Capsaicin with a low concentration (0.01 nM–0.01 µM) increased contractile frequency in both the colon and rectum of adult rats. However, the effect of capsaicin on frequency was abolished at higher concentrations (0.01 µM–3 µM). A capsaicin-evoked change in contractile frequency in adult rats was blocked by capsazepine and L-NAME. At lower concentrations (0.01 nM–0.01 µM), capsaicin did not show any change in frequency in the neonatal colon, while a decrease in contractile frequency was observed with the higher concentrations (0.1 µM–3 µM) of capsaicin. In neonates, capsazepine pre-treatment produced changes in frequency for both the colon and rectum. However, pre-application of L-NAME decreased frequency in the neonate rectum but not in the colon. Conclusion: Capsaicin-induced changes in contractile activity may or may not involve TRPV1 or the Nitric Oxide (NO) pathway, depending on the part of the large gut and developmental maturity.

5-HT3 receptors modulate changes in voiding pattern and bladder contractility in water avoidance stress-induced bladder overactivity in male mice.

Chronic psychological stress aggravates painful bladder syndrome symptoms. Previous studies suggest roles of 5-HT3 receptors in regulating micturition and bladder hypersensitivity. This study aimed to investigate the roles of 5-HT3 receptors in modulating voiding patterns and spontaneous bladder contractile properties in water avoidance stress-induced mice. Voiding patterns in sham stress (SS), water avoidance stress (WS), and water avoidance stress with daily oral gavage of ondansetron (1mg/kg BW) (WA) groups were analyzed after exposure to repeated water avoidance stress for 10days. Changes in contractile activity of isolated bladder in response to KCl, carbachol, and 5-hydroxytryptamine were determined. Bladder mast cell quantification was examined using toluidine blue staining. Urine voided area was significantly decreased in WS group after exposure to 10days of the stress protocol, which was reversed in the WA group. The WS group had a higher number of urine spots than the SS group. Increased mast cell degranulation was observed in the stressed mice. Bladder strips of the WS group showed higher tonic and amplitude of spontaneous contraction than the SS group, which were normalized by ondansetron administration. Increased response to carbachol-induced bladder contraction was observed in the bladder of stressed mice, which was attenuated with ondansetron pre-incubation. Water avoidance stress-induced mice exhibited changes in voiding pattern, which was reversed by oral administration with a 5-HT3 receptor antagonist (ondansetron). Enhanced contractile response to cholinergic stimulation in the urinary bladder of the psychological stress-induced bladder overactivity was mediated through 5-HT3 receptors.

Influence of conditioned media from glial cell cultures on contractility of uterine in rats of different ages

Background. The physiological regulation of the uterine contractile activity changes with age, which leads to an increased number of prolonged labor and emergency caesarean sections in women giving birth at the age of 35+. One of the modern approaches to correct the function of the reproductive system is the use of from cell cultures. CM from glial cell culture contains neurotrophic factors that play an important role in maintaining the contractile function of the uterus. Current cell culture technologies include cryopreservation.Objective: to research experimentally the effect of CM obtained from intact and cryopreserved cultures of glial cells on the contractile activity of the uterus in rats of different reproductive ages.Materials and methods. The monolayer cell culture was obtained from the dorsal root ganglia of neonatal piglets and cryopreserved in the presence of cryoprotectant dimethyl sulfoxide. CM from native and cryopreserved cultures were collected for 28 days, after which fractions with a molecular weight of < 30 kDa were obtained from them by ultrafiltration. Rats at the age of 6 and 14 months, which corresponds to reproductive age and late reproductive age (LRA), were intraperitoneally injected with 0.2 ml of media from intact (ICM) or cryopreserved (CCM) cultures for 9 days. On the 30th – 32nd day after the end of the administration of CM animals were slaughtered and the uterine contractile activity was determined by the organ bath method, the relative area of myometrium and density of myocytes by histological method, the average area of labeling with specific antibodies to smooth muscle actin by immunohistochemical method. The statistical significance of differences was assessed by the Mann–Whitney test.Results. It was found that spontaneous, OT-, and KCl-induced tension of isometric contraction of the uterus in intact LRA rats decreased by 19, 20, and 14%, respectively, compared with intact reproductive aged animals. After the introduction of ICM and CCM in LRA animals, normalization of isometric contraction parameters was observed. This effect was realized against the background of an increase in the area of the myometrium, the density of myocytes, and actin expression.Conclusions. Intra-abdominal administration of CM from glial cell culture increases the uterine contractile activity in LRA rats. This effect is realized by increasing the relative area of the myometrium, the density of myocytes, and the area of expression of smooth muscle actin. The effect of media from intact and cryopreserved cultures on the contractile activity of the uterus was similar, which makes it possible to use low-temperature culture storage technologies to obtain CM without losing its biological effect.

Contractile Activity of Lymph Nodes in Young, Middle-Aged, and Old Rats.

We studied age-associated changes in contractile activity of isolated cervical and mesenteric lymph nodes in rats. In young and middle-aged rats, no significant changes in contractile activity of lymph nodes were revealed. In old rats, the amplitude of spontaneous contractions of lymph nodes was lower and their rate was higher than in young and middle-aged animals; the sensitivity of lymph nodes to vasoactive agents was reduced and the threshold of the response was higher in old rats.

Comparison of inhibitory neuromuscular transmission in the Cynomolgus monkey IAS and rectum: special emphasis on differences in purinergic transmission.

Inhibitory neuromuscular transmission (NMT) was compared in the internal anal sphincter (IAS) and rectum of the Cynomolgus monkey, an animal with high gene sequence identity to humans. Nitrergic NMT was present in both muscles while purinergic NMT was limited to the rectum and VIPergic NMT to the IAS. The profile for monkey IAS more closely resembles humans than rodents. In both muscles, SK3 channels were localized to PDGFRα+ cells that were closely associated with nNOS+ /VIP+ nerves. Gene expression levels of P2RY subtypes were the same in IAS and rectum while KCNN expression levels were very similar. SK3 channel activation and inhibition caused faster/greater changes in contractile activity in rectum than IAS. P2Y1 receptor activation inhibited contraction in rectum while increasing contraction in IAS. The absence of purinergic NMT in the IAS may be due to poor coupling between P2Y1 receptors and SK3 channels on PDGFRα+ cells. Inhibitory neuromuscular transmission (NMT) was compared in the internal anal sphincter (IAS) and rectum of the Cynomolgus monkey, an animal with a high gene sequence identity to humans. Electrical field stimulation produced nitric oxide synthase (NOS)-dependent contractile inhibition in both muscles whereas P2Y1-dependent purinergic NMT was restricted to rectum. An additional NOS-independent, α-chymotrypsin-sensitive component was identified in the IAS consistent with vasoactive intestinal peptide-ergic (VIPergic) NMT. Microelectrode recordings revealed slow NOS-dependent inhibitory junction potentials (IJPs) in both muscles and fast P2Y1-dependent IJPs in rectum. The basis for the difference in purinergic NMT was investigated. PDGFRα+ /SK3+ cells were closely aligned with nNOS+ /VIP+ neurons in both muscles. Gene expression of P2RY was the same in IAS and rectum (P2RY1>>P2RY2-14) while KCNN3 expression was 32% greater in rectum. The SK channel inhibitor apamin doubled contractile activity in rectum while having minimal effect in the IAS. Contractile inhibition elicited with the SK channel agonist CyPPA was five times faster in rectum than in the IAS. The P2Y1 receptor agonist MRS2365 inhibited contraction in rectum but increased contraction in the IAS. In conclusion, both the IAS and the rectum have nitrergic NMT whereas purinergic NMT is limited to rectum and VIPergic NMT to the IAS. The profile in monkey IAS more closely resembles that of humans than rodents. The lack of purinergic NMT in the IAS cannot be attributed to the absence of PDGFRα+ cells, P2Y1 receptors or SK3 channels. Rather, it appears to be due to poor coupling between P2Y1 receptors and SK3 channels on PDGFRα+ cells.

PL-008 Adaptation of skeletal muscle to aerobic exercise: specific transcriptome response to acute exercise and training

Objective Variety of processes including circadian rhythm and systemic factors affect expression of many genes in skeletal muscle during a day. Therefore, post-exercise gene expression depends on many factors: contractile activity per seas well as circadian rhythm, nerve activity, concentration of different substances in blood, feeding and fasting. In our study, we investigated specific for contractile activity changes in the transcriptome in untrained and trained (after an aerobic training programme) human skeletal muscle. The second goal was to examine effect of aerobic training on gene expression in muscle in basal state.
 Methods Seven untrained males performed the one-legged knee extension exercise (for 60 min) with the same relative intensity before and after a 2 month aerobic training programme (1 h/day, 5/week). Biopsy samples were taken at rest (basal state, 48 h after the previous exercise), 1 and 4 h after one-legged exercise from m. vastus lateralisof either leg. This approach allowed us to evaluate specific changes in the transcriptome associated with contractile activity. RNA­sequencing (84 samples in total; ~42 million reads/sample) was performed by HiSeq 2500 (Illumina).
 Results Two months aerobic training increased the aerobic capacity of the knee-extensor muscles (power at anaerobic threshold in incremental one-legged and cycling tests), the maximum rate of ADP-stimulated mitochondrial respiration in permeabilized muscle fibres and amounts of oxidative phosphorylation proteins. After one-legged exercise, expression of many genes was changed in exercised muscle (~1500) as well as in non-exercised muscle (~400). Pronounced changes in gene expression in non-exercised muscle may be associated with many factors, including circadian rhythm (result of GO analysis).
 To examine transcriptome changes specific for contractile activity, the difference in gene expression between legs was examined. In untrained muscle, one-legged exercise changed expression of ~1200 genes specific for contractile activity at each time point. Despite the same relative intensity of one-legged exercise, transcriptomic response in trained muscle was markedly lower (~300 genes) compare to untrained.
 We observed a strong overlap between transcriptomic responses (~250 genes) and particularly between enriched transcription factor binding sites in promoters of these genes in untrained and trained muscles. These sets of genes and transcription factors play the key role in adaptation of muscle to contractile activity independently on the level of muscular fitness.
 Surprisingly, 2 months aerobic training changed the expression of more than 1500 genes in basal state. Noteworthy, these genes demonstrated a small overlap (~200 genes) with genes related to specific response to acute exercise. Moreover, these genes were associated with significantly different biological processes than genes related to specific response to acute exercise.
 Conclusions Specific for contractile activity changes in the transcriptome in untrained and trained human skeletal muscle were revealed for the first time. After 2 month aerobic training, the specific transcriptome response to acute exercise become much less pronounced. A computational approach reveals common transcription factors important for adaptation of both untrained and trained muscle. We found out that adaptation of muscle to aerobic training associates not only with the transitory changes in gene expression after each exercise, but also with the marked changes in transcriptome in basal state.
 This work was supported by the Russian Science Foundation (14­15­00768).

Heart mechanical and hemodynamic parameters of a beetle, Tenebrio molitor, at selected ages.

The physiological processes that occur during the aging of insects are poorly understood. The aim of this study was to describe the changes in contractile activity and hemodynamic parameters of the heart that take place as the coleopteran beetle, Tenebrio molitor, ages. The frequency of heart contractions in beetles that had just undergone metamorphosis (median 24.7 beats/min) was significantly lower than the frequency of heart contractions in older beetles. In 56% of beetles that were<1week of age, a pattern of contractile activity with alternating periods of higher and lower contraction frequency was detected, suggesting that some posteclosion developmental processes occur during the first week of adulthood. All beetles that were 1week of age showed a regular rhythm of heart contractions (median 72 beats/min). In older beetles, abnormalities such as heart arrhythmias or heart arrest were observed. The incidence of arrhythmia as well as the arrhythmicity index was highest in beetles that were 8-18weeks old. The calculated stroke volume (SV) was also found to increase from eclosion to 12weeks of age, and then decreased as adults aged further. Interestingly, cardiac output increased gradually, but the ejection fraction did not change significantly with age.

Successive contractile periods activate mitochondria at the onset of contractions in intact rat cardiac trabeculae.

The rate of oxidative phosphorylation depends on the contractile activity of the heart. Cardiac mitochondrial oxidative phosphorylation is determined by free ADP concentration, mitochondrial Ca2+ accumulation, mitochondrial enzyme activities, and Krebs cycle intermediates. The purpose of the present study was to examine the factors that limit oxidative phosphorylation upon rapid changes in contractile activity in cardiac muscle. We tested the hypotheses that prior contractile performance enhances the changes in NAD(P)H and FAD concentration upon an increase in contractile activity and that this mitochondrial "priming" depends on pyruvate dehydrogenase activity. Intact rat cardiac trabeculae were electrically stimulated at 0.5 Hz for at least 30 min. Thereafter, two equal bouts at elevated stimulation frequency of 1, 2, or 3 Hz were applied for 3 min with 3 min of 0.5-Hz stimulation in between. No discernible time delay was observed in the changes in NAD(P)H and FAD fluorescence upon rapid changes in contractile activity. The amplitudes of the rapid changes in fluorescence upon an increase in stimulation frequency (the on-transients) were smaller than upon a decrease in stimulation frequency (the off-transients). A first bout in glucose-containing superfusion solution resulted, during the second bout, in an increase in the amplitudes of the on-transients, but the off-transients remained the same. No such priming effect was observed after addition of 10 mM pyruvate. These results indicate that mitochondrial priming can be observed in cardiac muscle in situ and that pyruvate dehydrogenase activity is critically involved in the mitochondrial adaptation to increases in contractile performance. NEW & NOTEWORTHY Mitochondrial respiration increases with increased cardiac contractile activity. Similar to mitochondrial "priming" in skeletal muscle, we hypothesized that cardiac mitochondrial activity is altered upon successive bouts of contractions and depends on pyruvate dehydrogenase activity. We found altered bioenergetics upon repeated contractile periods, indicative of mitochondrial priming in rat myocardium. No effect was seen when pyruvate was added to the perfusate. As such, pyruvate dehydrogenase activity is involved in the mitochondrial adaptation to increased contractile performance.

Regulation of Contractile Responses of Vascular Smooth Muscle Cells under Conditions of Hypoxia-Reoxygenation.

We analyzed the effects of hypoxia and reoxygenation on changes in contractile activity in rat aortic smooth muscles. Both hypoxia and reoxygenation induced relaxation of smooth muscle cells precontracted with high-potassium Krebs solution (30 mM KCl) or α1-adrenoceptor agonist phenylephrine. Vasodilation resulted from enhancement of potassium permeability of smooth muscle cell membranes caused by activation of voltage-gated potassium channels (triggered by both precontracting agents) or by opening of ATP-sensitive potassium channels (phenylephrine). In isolated smooth muscle cells, both hypoxia and inhibition of Na+,K+-ATPase with ouabain led to depletion of intracellular store of macroergic substances, reduced potassium concentration, and elevated the content of sodium ions.

Disorders of gastrointestinal hypomotility.

Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases.

Conscious voiding during bladder obstruction in guinea pigs correlates with contractile activity of isolated bladders.

There are many hypotheses accounting for detrusor overactivity; however, the exact mechanisms are still incompletely understood. We used a model of bladder outlet obstruction in male guinea pigs as a way to produce detrusor overactivity. The objective was to determine whether changes in voiding of obstructed guinea pigs correlates with specific changes in contractile activity of their isolated bladders in vitro. Conscious voiding activity of sham-operated and obstructed animals was measured in metabolic cages. Contractile activity (spontaneous or evoked by distension, electrical field stimulation or cholinergic agonists) was recorded via a pressure transducer in the isolated bladders in vitro. The frequency of conscious voiding increased (while voiding volume decreased) in the obstructed group, compared with the sham-operated group, 4 weeks after surgical intervention. In comparison to the sham-operated animals, the bladders from the obstructed guinea pigs were enlarged and inflamed, their frequency of spontaneous contractions was higher, while the amplitudes of electrical field stimulation (EFS)-induced contractions and bladder compliance were lower. Changes in conscious voiding during obstruction were significantly associated with alterations in structural parameters (bladder weight, thickness and histological damage score) and functional contractile parameters (frequency of spontaneous contractions, amplitude of EFS-induced contractions and bladder compliance) of their isolated bladders. Our findings revealed significant association between conscious voiding and structural and contractile activity changes of the isolated bladders in obstruction. The data suggest that change in contractile activity of the bladder itself is a major contributor to obstruction-induced bladder overactivity.

Changes in Contractile Activity of the Large Intestine in Rabbits during the Poststress Period before and after Blockade of Muscarinic and Nicotinic Receptors

The rabbits were exposed twice to stress, fixation to a frame in the supine position, for 60 min. Contractile activity of all portions of the large intestine was shown to increase significantly during the poststress period. These changes were not observed under conditions of blockade of muscarinic and nicotinic receptors. This state can be considered as dyskinesia impairing large intestinal transit of chyme.

Changes in Contractile Activity of Rabbit Colon under Stress Conditions and during Post-Stress Period before and after Blockade of Muscarinic and Nicotinic Cholinergic Receptors

Psychogenic stress in rabbits induced by fixation of the animal to a frame was accompanied by an increase in contractile activity of the initial portion of the distal colon, which was abolished by blockade of muscarinic and nicotinic cholinergic receptors. Increased contractile activity of the colon was due to centrogenic stimulation of preganglionic neurons of the parasympathetic nervous system followed by the involvement of the effector cholinergic neurons of the enteric nervous system into excitation.

Influence of nanosized magnetite on the contractile activity of smooth muscle segments of the pulmonary artery of guinea pigs

This study investigates the contractile activity of smooth muscle segments of guinea pig pulmonary artery by the method of mechanografy and morphological picture of lungs, airways and blood vessels of the pulmonary circulation under the influence of nanosized magnetite. It is shown that chronic inhalation intake of magnetite nanoparticles has a cytotoxic effect, leading to inflammatory changes in the airways, lung parenchyma and pulmonary vessels, as well as a change in contractile activity of the pulmonary artery by the action of neurotransmitters and mediators of exercising their functions under physiological conditions or produced during the inflammatory the process.

Changes in Contractile Activity of the Duodenum, Jejunum, and Ileum under Conditions of Psychogenic Stress in Rabbits

Psychogenic stress in rabbits caused by fixation of the animal to a frame was accompanied by an increase in duodenal contractile activity. In the jejunum, initial inhibition of motor activity gave way to activation more pronounced in the proximal part. In both parts of the ileum, inhibition of contractile activity was noted. A proximodistal gradient of the excitatory and inhibitory effects on the motility of the small intestine was demonstrated.

Melatonin reverses urinary system and aorta damage in the rat due to chronic nicotine administration

We have evaluated the changes in contractile activity and oxidant damage of corpus cavernosum, urinary bladder, kidney and aorta after chronic nicotine administration in rats. The effects of melatonin on these parameters were investigated also. Male Wistar albino rats were injected intraperitoneally with nicotine hydrogen bitartrate (0.6 mg kg(-1) daily for 21 days) or saline. Melatonin (10 mg kg(-1), i.p.) was administered either alone or with nicotine injections. Corpus cavernosum, bladder and aorta were used for contractility studies, or stored with kidneys for the measurement of malondialdehyde and glutathione levels. Corpus cavernosum, bladder, and aorta samples were examined histologically and the extent of microscopic tissue damage was scored. In the nicotine-treated group, the contraction of corpus cavernosum, bladder and aorta samples and the relaxation of corporeal and aorta tissues decreased significantly compared with controls. However, melatonin treatment restored these responses. In the nicotine-treated group, there was a significant increase in the malondialdehyde levels of the corporeal tissue, bladder, kidney and aorta, with marked reductions in glutathione levels compared with controls. Melatonin treatment reversed these effects also. Melatonin administration to nicotine-treated animals caused a marked reduction in the microscopic damage of the tissues compared with those of the untreated group. In this study, nicotine-induced dysfunction of the corpus cavernosum, bladder and aorta of rats was reversed by melatonin treatment. Moreover, melatonin, as an antioxidant, abolished elevation in lipid peroxidation products, and reduction in the endogenous antioxidant glutathione, and protected the tissues from severe damage due to nicotine exposure.

W2053 The Impact of Using Different Standardized Meals in the Assessment of Motility of Upper Gastrointestinal Tract

Introduction: Motor functions of the stomach have traditionally been regarded to differ by stomach region. However, to date there have been few studies on the gastric contractility of the human stomach. Objectives: The aim of the present study was therefore to examine the response to acetylcholine and electrical field stimulation (EFS) of the human fundus, corpus and antrum. Methods: Gastric muscles were obtained from 71 patients (44 males, 27 females with an average age of 60.7 yrs; 34 85 yrs) undergoing gastric cancer surgery. Muscle strips (n = 71) were isolated and attached to a fixed mount and to an isometric strain gauge. The muscle strips were studied In Vitro for their contractile responses to acetylcholine (n=25) and electrical field stimulation (EFS, n=46). N-nitro-L-arginine (L-NA), atropine and tetrodotoxin (TTX) were added to assess the nitro oxide-mediated changes and cholinergic neural pathway involved in EFS-induced contractions. Results: Spontaneous contractile activity was observed in muscle strips of stomach regions. In the antrum, acetylcholine induced increase in contraction frequency and peak contraction in dose dependent pattern, but no significant change was noticed in muscle tone. In corpus and fundus, acetylcholine induced dose-dependent increase in peak contraction and muscle tone, but there was no significant change in frequency. The response to EFS also differed by stomach region. EFS produced no significant change in contractile activity in 22 of 46 muscle strips. When EFS evoked frequency-dependent contraction or relaxation in muscle strips, contraction was primarily observed in the muscle strips from the antrum, and relaxation was primarily observed in the muscle strips of the corpus and fundus. The addition of LNA (100 uM) to the muscle bath converted the EFS-induced relaxation to contractions and increased the EFS-induced contractions. EFS-induced contractions were abolished by atropine (1uM) or TTX (1uM). Conclusions: Our study demonstrated that the response to acetylcholine and electrical field stimulation on human gastric fundus and corpus is different with that of human gastric antrum.

W2052 Urocortin Reduces Food Intake via Inhibition of Ghrelin Secretion in Rats

Introduction: Motor functions of the stomach have traditionally been regarded to differ by stomach region. However, to date there have been few studies on the gastric contractility of the human stomach. Objectives: The aim of the present study was therefore to examine the response to acetylcholine and electrical field stimulation (EFS) of the human fundus, corpus and antrum. Methods: Gastric muscles were obtained from 71 patients (44 males, 27 females with an average age of 60.7 yrs; 34 85 yrs) undergoing gastric cancer surgery. Muscle strips (n = 71) were isolated and attached to a fixed mount and to an isometric strain gauge. The muscle strips were studied In Vitro for their contractile responses to acetylcholine (n=25) and electrical field stimulation (EFS, n=46). N-nitro-L-arginine (L-NA), atropine and tetrodotoxin (TTX) were added to assess the nitro oxide-mediated changes and cholinergic neural pathway involved in EFS-induced contractions. Results: Spontaneous contractile activity was observed in muscle strips of stomach regions. In the antrum, acetylcholine induced increase in contraction frequency and peak contraction in dose dependent pattern, but no significant change was noticed in muscle tone. In corpus and fundus, acetylcholine induced dose-dependent increase in peak contraction and muscle tone, but there was no significant change in frequency. The response to EFS also differed by stomach region. EFS produced no significant change in contractile activity in 22 of 46 muscle strips. When EFS evoked frequency-dependent contraction or relaxation in muscle strips, contraction was primarily observed in the muscle strips from the antrum, and relaxation was primarily observed in the muscle strips of the corpus and fundus. The addition of LNA (100 uM) to the muscle bath converted the EFS-induced relaxation to contractions and increased the EFS-induced contractions. EFS-induced contractions were abolished by atropine (1uM) or TTX (1uM). Conclusions: Our study demonstrated that the response to acetylcholine and electrical field stimulation on human gastric fundus and corpus is different with that of human gastric antrum.