Guinea-pig Intestine Research Articles

Probiotic capacity of commensal lactic acid bacteria from the intestine of Guinea pigs (Cavia porcellus)

The intricate balance of intestinal microbiota is significantly influenced by the pivotal role of indigenous lactic acid bacteria (LAB). These LAB not only contribute to antimicrobial activity and enhance animal health and productivity but also serve as defense against intestinal infections. In the present study, the probiotic potential of LAB strains isolated from various intestinal sections of adult and young guinea pigs (Cavia porcellus) was comprehensively assessed. Strains belonging to the genera Ligilactobacillus, Weissella, Enterococcus, and Limosilactobacillus were also identified. The antibacterial activities of the LAB strains against Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus were quantified. Exopolysaccharide production, adherence capacity, antibiotic resistance, and bile salt tolerance (0.15 %, 0.30 %, and 0.45 %) of LAB were quantified. Further analyses focused on the effects of pH (2.9, 5.0, 6.4, and 7.4), temperature (40, 50, and 60 °C) and NaCl concentrations (3.5 % and 6.5 % w/v) on LAB growth. Strains GCI9 and GDE10 (Ligilactobacillus salivarius), isolated from the cecum and intestine of guinea pigs, exhibited significant antimicrobial activity against S. typhimurium, E. coli and S. aureus. Remarkable adherence capacity to porcine gastric mucin was demonstrated by L. salivarius strains, specifically ACI1, GCI9, and GDE10, with the highest exopolysaccharide levels produced by ACI1 and GCI9 (1.71 and 1.76 mg/mL, respectively). The probiotic potential was further underscored by remarkable bile salt tolerance, especially in strain GDE10, and substantial exopolysaccharide production. These strains displayed notable adaptability to varying environmental conditions, including NaCl concentrations at 3.5 % and 6.5 %, temperatures ranging from 40 to 60 °C, and pH levels of 2.9, 5.0, 6.4, and 7.4. This comprehensive assessment of the probiotic properties of L. salivarius strains, particularly ACI1, GCI9, and GDE10, shows promise for the development of probiotic formulations aimed at enhancing the intestinal health of guinea pigs.

Mucous non-goblet cells in the small intestine of guinea pigs (Cavia porcellus): a histological and histochemical study.

The covering and glandular epithelium of the small intestine in guinea pigs (Cavia porcellus) include some mucus-secreting cells. Goblet cells are specific cells for mucus secretion with a distinctive cup-like appearance due to the accumulation of mucin in the apical pole. The deep crypt secretory (DCS) cells were identified in a limited array of species and only recently were noticed in the large intestine in mice, guinea pigs, humans, monkeys, and pigs. Our study focuses on the microscopical and histochemical features of the DCS cells in the small intestine of guinea pigs. The samples from the small intestine were collected from five fully grown guinea pigs that were presented to the Hospital of the Faculty of Veterinary Medicine Cluj-Napoca (Romania) with severe lesions resulted from domestic activities. The collected tissue samples underwent fixation in 10% buffered formalin and were later processed by standard paraffin technique. Mucous substances were detected using the Periodic Acid-Schiff and Alcian-Blue histochemical stain methods. The intestinal samples of the guinea pigs assessed had a standard microanatomical structure. As regards the mucous-secreting cells from the small intestine, two cell types were identified, i.e. the goblet cells and DCS cells. DCS cells were only detected in the deep parts of the Lieberkühn glands from the jejunum and ileum, and were different morphologically and histochemically from the regular goblet cells. Our study managed to describe for the first time in guinea pigs, the existence of DCS cells in the jejunum and ileum of the small intestine, but not in the duodenum.

Histological structure and evaluation of cellular layers of Large intestine in Guinea pig (Cavia porcellus)

The Aim of this study is to determine the histological structure in the wall layers of large intestine of guinea pig. The cecum and colon was characterized by a delicate lining that is moisturized by mucus and also by a gel that is a by-product of bacterial fermentation. This study was performed on the cecum and ascending and descending colon in five health animals. The cecum and colon wall was composed of four tunicae (mucosa, submucosa, muscularis and serosa, the tunica mucosa consist of epithelium, lamina propria and muscularis mucosa. The colon lumen lined by simple columnar epithelium with prominent goblet cells. The epithelial surface of the colon is covered by the openings of tubular intestinal glands which penetrate deep into the thick mucosa. The glands consist of absorptive cells that absorb water and salt, goblet cells were secrete the mucus, and scattered Paneth cells. Crypts of Lie beckon (intestinal glands) are a simple tubular glands is observe in most mammals, which extending from the muscularis mucosa through the thickness of the lamina propria and they open into the intestinal lumen. Muscularis mucosa, consisted of very thin two layers of inner circular and outer longitudinal smooth muscles, the greater thickness of the muscularis mucosa was in the adult type and the submucosa was consists of dense a irregular connective tissue. The muscular layer is consists of internal circular and external longitudinal layers of smooth muscles, which mean their thickness is decreased toward the last parts. Thus, the serous coat is a thin layer of loose connective tissue, the thickness was decreases toward the last parts.

Studying the Effectiveness of Anise Extract and Alignite Nanoparticles on the Balance of the Microbial Gut Flora and Some Immunological Parameters in the Laboratory Guinea Pigs

The study aims to determine the effect of oral dosage of anise fruit alcoholic extract and Alignite Nanoparticles (AlgNPs) and their interaction with the antibiotics Cefotaxime and Metronidazole concerning the parameters related to the balance of intestine normal flora with some immunological parameters in laboratory guinea pigs induced with diarrhea by E.coli. The results show that the Enterobacteriaceae bacterial colonies counts belonging less than those accounts of lactic acid bacteria in the intestines of laboratory guinea pigs. It is also found that the synergistic action of the nanocomposites with different antibiotics like what: have a better antimicrobial effect than the effect of each individually. There is also a significant increase (p<0.05) in the IgM and IgA values, which are at 1789 and 362 ng/L, respectively compared with their levels in the control group animals which are at 1230 and 184.5 (ng/L), respectively. The value of IgG does not change significantly in the oral dosage of the extract or the AlgNPs. After the recovery status of laboratory animals from infection, the level of IgG increased significantly, which gives evidence of bacterial infection in the infected animals.

Antispasmodic, antidepressant and anxiolytic effects of extracts from Schinus lentiscifolius Marchand leaves

Schinus lentiscifolius (Anacardiaceae) is widely used in folk medicine for treating gastrointestinal and emotional complaints but there are no scientific studies that support these uses. This work aims at evaluating the antispasmodic and central effects of S. lentiscifolius as well as the flavonoids presence in the tincture (SchT) and the composition of the essential oil (SchO). SchT inhibited the concentration-response curves (CRC) of carbachol and calcium in a non-competitive way in isolated rat intestine, bladder and uterus. SchT also non-competitively inhibited the CRC of histamine in guinea-pig intestine and the CRCs of serotonin and oxytocin in rat uterus. Isoquercetin and rutin were identified in SchT. The behavioral effects of SchT, SchO and infusion of S. lentiscifolius leaves (SchW) were tested in mice. These extracts showed an anxiolytic-like effect in the novelty-suppressed feeding test, which was reversed by flumazenil except in SchO-treated mice. Only SchO reduced the spontaneous locomotor function in the open field test. Also, SchT and SchW decreased immobility time in both, the tail suspension (TST) and forced swimming tests, while SchO produced the same effect in the TST. d-limonene and α-santalol were the main components found in SchO. The results demonstrated that extracts obtained from S. lentiscifolius leaves were effective as intestinal, urinary and uterine antispasmodics. SchT and SchW exhibited anxiolytic and antidepressant properties without sedation, whereas SchO showed also sedative properties. Therefore, the present study gives preclinical support to the traditional use of this plant for gastrointestinal and depressive or emotional symptoms.

Токсигенність штамів yersinia еnterocolitica, ізольованих з різних об’єктів

Токсигенність штамів yersinia еnterocolitica, ізольованих з різних об’єктів

Species-Specific Glucose-6-Phosphatase Activity in the Small Intestine-Studies in Three Different Mammalian Models.

Besides the liver, which has always been considered the major source of endogenous glucose production in all post-absorptive situations, kidneys and intestines can also produce glucose in blood, particularly during fasting and under protein feeding. However, observations gained in different experimental animals have given ambiguous results concerning the presence of the glucose-6-phosphatase system in the small intestine. The aim of this study was to better define the species-related differences of this putative gluconeogenic organ in glucose homeostasis. The components of the glucose-6-phosphatase system (i.e., glucose-6-phosphate transporter and glucose-6-phosphatase itself) were analyzed in homogenates or microsomal fractions prepared from the small intestine mucosae and liver of rats, guinea pigs, and humans. Protein and mRNA levels, as well as glucose-6-phosphatase activities, were detected. The results showed that the glucose-6-phosphatase system is poorly represented in the small intestine of rats; on the other hand, significant expressions of glucose-6-phosphate transporter and of the glucose-6-phosphatase were found in the small intestine of guinea pigs and homo sapiens. The activity of the recently described fructose-6-phosphate transporter–intraluminal hexose isomerase pathway was also present in intestinal microsomes from these two species. The results demonstrate that the gluconeogenic role of the small intestine is highly species-specific and presumably dependent on feeding behavior (e.g., fructose consumption) and the actual state of metabolism.

Mapping of Shigella flexneri's tissue distribution and type III secretion apparatus activity during infection of the large intestine of guinea pigs.

ABSTRACT Shigella spp. are bacterial pathogens that invade the human colonic mucosa using a type III secretion apparatus (T3SA), a proteinaceous device activated upon contact with host cells. Active T3SAs translocate proteins that carve the intracellular niche of Shigella spp. Nevertheless, the activation state of the T3SA has not been addressed in vivo. Here, we used a green fluorescent protein transcription-based secretion activity reporter (TSAR) to provide a spatio-temporal description of S. flexneri T3SAs activity in the colon of Guinea pigs. First, we observed that early mucus release is triggered in the vicinity of luminal bacteria with inactive T3SA. Subsequent mucosal invasion showed bacteria with active T3SA associated with the brush border, eventually penetrating into epithelial cells. From 2 to 8 h post-challenge, the infection foci expanded, and these intracellular bacteria displayed homogeneously high-secreting activity, while extracellular foci within the lamina propria featured bacteria with low secretion activity. We also found evidence that within lamina propria macrophages, bacteria reside in vacuoles instead of accessing the cytosol. Finally, bacteria were cleared from tissues between 8 and 24 h post-challenge, highlighting the hit-and-run colonization strategy of Shigella. This study demonstrates how genetically encoded reporters can contribute to deciphering pathogenesis in vivo.

E. coli O124 K72 alters the intestinal barrier and the tight junctions proteins of guinea pig intestine

Our research group previously isolated and identified a strain of pathogenic Escherichia coli from clinical samples called E. coli O124 K72. The present study was aimed at determining the potential effects of E. coli O124 K72 on intestinal barrier functions and structural proteins integrity in guinea pig.Guinea pigs were grouped into three groups; control (CG); E. coli O124 K72 (E. coli); and probiotics Lactobacillus rhamnosus (LGG). Initially, we create intestinal dysbiosis by giving all animals Levofloxacin for 10days, but the control group (CG) received the same volume of saline. Then, the animals received either E. coli O124 K72 (E. coli) or Lactobacillus rhamnosus (LGG) according to their assigned group. E. coli O124 K72 treatment significantly affected colon morphology and distorted intestinal barrier function by up-regulating Claudin2 and down-regulating Occludin. In addition, E. coli upregulated the mRNA expression of MUC1, MUC2, MUC13 and MUC15. Furthermore, suspected tumor was found in the E. coli treated animals. Our results suggested that E. coli O124 K72 strain has adverse effects on intestinal barrier functions and is capable of altering integrity of structural proteins in guinea pig model while at same time it may have a role in colon carcinogenesis.

Characterization of a biofilm-forming Shigella flexneri phenotype due to deficiency in Hep biosynthesis.

Deficiency in biosynthesis of inner core of lipopolysaccharide (LPS) rendered a characteristic biofilm-forming phenotype in E. coli. The pathological implications of this new phenotype in Shigella flexneri, a highly contagious enteric Gram-negative bacteria that is closely related to E. coli, were investigated in this study. The ΔrfaC (also referred as waaC) mutant, with incomplete inner core of LPS due to deficiency in Hep biosynthesis, was characteristic of strong biofilm formation ability and exhibited much more pronounced adhesiveness and invasiveness to human epithelial cells than the parental strain and other LPS mutants, which also showed distinct pattern of F-actin recruitment. Failure to cause keratoconjunctivitis and colonize in the intestine in guinea pigs revealed that the fitness gain on host adhesion resulted from biofilm formation is not sufficient to offset the loss of fitness on survivability caused by LPS deletion. Our study suggests a clear positive relationship between increased surface hydrophobicity and adhesiveness of Shigella flexneri, which should be put into consideration of virulence of Shigella, especially when therapeutic strategy targeting the core oligosaccharide (OS) is considered an alternative to deal with bacterial antibiotics-resistance.

Serotonin or the Mucosa Do Not Mediate the Motor Effect of Allyl Isothiocyanate in the Guinea-Pig Small Intestine

Background: Serotonin (5-hydroxytryptamine, 5-HT), originating from the enterochromaffin cells has been reported to mediate the contractile effect of the sensory stimulant and TRPA1 activator allyl isothiocyanate (AITC) in the guinea-pig small intestine [Nozawa et al: Proc Natl Acad Sci U S A 2009;106:3408-3413]. Summary: In the present experiments, the nerve-mediated contraction of this preparation due to AITC was not inhibited by a combination of methysergide (broad-spectrum 5-HT antagonist; 0.3 µmol/l), Y 25130 (azasetron, 5-HT₃ receptor antagonist; 1 µmol/l) and SB 204070 (5-HT₄ receptor antagonist; 2 µmol/l) or by 5-HT receptor desensitization, that is, pretreatments that practically abolished contractions of similar size in response to exogenous 5-HT, without causing nonspecific effects. AITC also contracted longitudinal muscle-myenteric plexus preparations, an effect also fully resistant to the combination of 5-HT receptor antagonists. The pharmacology of AITC in strip preparations matched that in the whole ileum. Key Messages: It is concluded that neither endogenous 5-HT nor the gut mucosa contributes to the excitatory effect of AITC in the guinea-pig small intestine. The combination of 5-HT antagonists elaborated is suitable for studying the possible involvement of 5-HT in motor responses of the guinea-pig intestine.

L-dehydroascorbic acid can substitute l-ascorbic acid as dietary vitamin C source in guinea pigs

Vitamin C deficiency globally affects several hundred million people and has been associated with increased morbidity and mortality in numerous studies. In this study, bioavailability of the oxidized form of vitamin C (l-dehydroascorbic acid or DHA)—commonly found in vitamin C containing food products prone to oxidation—was studied. Our aim was to compare tissue accumulation of vitamin C in guinea pigs receiving different oral doses of either ascorbate or DHA. In all tissues tested (plasma, liver, spleen, lung, adrenal glands, kidney, muscle, heart, and brain), only sporadic differences in vitamin C accumulation from ascorbate or DHA were observed except for the lowest dose of DHA (0.25mg/ml in the drinking water), where approximately half of the tissues had slightly yet significantly less vitamin C accumulation than from the ascorbate source. As these results contradicted data from rats, we continued to explore the ability to recycle DHA in blood, liver and intestine in guinea pigs, rats and mice. These investigations revealed that guinea pigs have similar recycling capacity in red blood cells as observed in humans, while rats and mice do not have near the same ability to reduce DHA in erythrocytes. In liver and intestinal homogenates, guinea pigs also showed a significantly higher ability to recycle DHA compared to rats and mice. These data demonstrate that DHA in guinea pigs—as in humans—is almost as effective as ascorbate as vitamin C source when it comes to taking up and storing vitamin C and further suggest that the guinea pig is superior to other rodents in modeling human vitamin C homeostasis.

Mechanical stress activates neurites and somata of myenteric neurons.

The particular location of myenteric neurons, sandwiched between the 2 muscle layers of the gut, implies that their somata and neurites undergo mechanical stress during gastrointestinal motility. Existence of mechanosensitive enteric neurons (MEN) is undoubted but many of their basic features remain to be studied. In this study, we used ultra-fast neuroimaging to record activity of primary cultured myenteric neurons of guinea pig and human intestine after von Frey hair evoked deformation of neurites and somata. Independent component analysis was applied to reconstruct neuronal morphology and follow neuronal signals. Of the cultured neurons 45% (114 out of 256, 30 guinea pigs) responded to neurite probing with a burst spike frequency of 13.4 Hz. Action potentials generated at the stimulation site invaded the soma and other neurites. Mechanosensitive sites were expressed across large areas of neurites. Many mechanosensitive neurites appeared to have afferent and efferent functions as those that responded to deformation also conducted spikes coming from the soma. Mechanosensitive neurites were also activated by nicotine application. This supported the concept of multifunctional MEN. 14% of the neurons (13 out of 96, 18 guinea pigs) responded to soma deformation with burst spike discharge of 17.9 Hz. Firing of MEN adapted rapidly (RAMEN), slowly (SAMEN), or ultra-slowly (USAMEN). The majority of MEN showed SAMEN behavior although significantly more RAMEN occurred after neurite probing. Cultured myenteric neurons from human intestine had similar properties. Compared to MEN, dorsal root ganglion neurons were activated by neurite but not by soma deformation with slow adaptation of firing. We demonstrated that MEN exhibit specific features very likely reflecting adaptation to their specialized functions in the gut.

Altered Gastrointestinal Motility in a Mouse Model of Multiple Sclerosis

Multiple sclerosis (MS) patients often experience constipation, but the etiology of this symptom is unknown. To study this in an animal model, we tested the hypothesis that mice with experimental autoimmune encephalomyelitis (EAE) would exhibit altered gastrointestinal (GI) transit and they would have circulating antibodies directed against targets in enteric ganglia. EAE was induced in C57BL/6J mice by injection of complete Freund's adjuvant (CFA) and myelin oligodendrocyte glycoprotein. After somatic motor symptoms developed, small intestinal transit was measured by calculating the leading edge (LE) and geometric center (GC) 20 minutes after oral gavage of rhodamine dextran. Whole GI transit time was determined by oral gavage of carmine red and timing the appearance in fecal pellets. Antibody targets were evaluated by immunohistochemical staining of guinea pig intestine with EAE and control plasma. Small intestinal transit was significantly slower in EAE mice than in controls (LE, p&lt;0.02; GC, p&lt;0.01), and was not altered in CFA controls. The rate of whole GI transit was significantly longer in EAE mice versus healthy controls (p&lt;0.05). Plasma from EAE mice yielded more intense immunoreactivity in myenteric ganglia than plasma from control animals, with immunostained structures including neurons and nerve processes. In summary, EAE is associated with slowed intestinal motility compared to healthy control mice, which could be representative of the bowel dysmotility exhibited by multiple sclerosis patients. The symptomology may involve the presence of enteric ganglion‐targeted antibodies in the blood of EAE mice. Funding: National MS Society

Toll-like receptor 4 contributes to the inhibitory effect of morphine on colonic motility in vitro and in vivo.

Opioids rank among the most potent analgesic drugs but gastrointestinal side effects, especially constipation, limit their therapeutic utility. The adverse effects of opioids have been attributed to stimulation of opioid receptors, but emerging evidence suggests that opioids interact with the innate immune receptor Toll-like receptor 4 (TLR4) and its signalling pathway. As TLR4 signalling affects gastrointestinal motility, we examined the involvement of TLR4 in morphine-induced depression of peristaltic motility in the guinea-pig intestine in vitro and male C57BL/6N mice in vivo. While the TLR4 antagonist TAK-242 (0.1 μM and 1 μM) did not alter the morphine-induced inhibition of peristalsis in the isolated guinea-pig small intestine, the morphine-induced decrease in pellet propulsion velocity in colonic segments was attenuated by TAK-242 (0.1 μM). The ability of TAK-242 (4 mg/kg) to mitigate the morphine-induced suppression of colonic motility was replicated in mice in vivo by measuring the expulsion time of beads inserted in the distal colon. The inhibition of upper gastrointestinal transit of mice by morphine was not affected by pre-treatment with TAK-242 (4 mg/kg) in vivo. This is the first report that morphine-induced inhibition of colonic peristalsis is alleviated by TLR4 antagonism. We therefore conclude that TLR4 may contribute to opioid-induced constipation.

Smooth Muscle-Depressant Activity of AP-18, a Putative TRPA1 Antagonist in the Guinea Pig Intestine

AP-18, a putative antagonist at TRPA1 receptor/ion channel, caused smooth muscle relaxation at 10-100 µmol/l. It inhibited cholinergic twitch responses evoked by electrical field stimulation of cholinergic nerves as well as contractions in response to acetylcholine and histamine in the guinea pig small intestine. AP-18 (30 µmol/l) blocked spontaneous contractions of longitudinal strips of human jejunum. It is concluded that AP-18 may have limited value in studying TRPA1-mediated responses in smooth muscles and should probably be used with care in other preparations because of possible nonspecific effects.

Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.

Paneth Cell Identification in the Small Intestine of Guinea Pig Offsprings (Cavia porcellus)

The aim of this study was to determine the presence, number, and morphometrical characteristics of Paneth cells (PC) in the small intestine of guinea pigs during lactation. We used 48 pups from 0 to 15 days old. Samples from small intestine were fixed in 10% buffered formaldehyde (pH 7.4) and processed for histological and morphometrical studies using hematoxylin and eosin (HE), Phloxine tartrazine or Masson's Trichome staining, or immunohistochemistry for lysozyme. PC were morphologically identified at day 2 using Masson's Trichome or Phloxine tartrazine stainings, and at day 4 using HE, whereas using immunohistochemistry they were recognized from birth. Morphometrical differences were found between the intestinal sections at each age studied, and within each section during the first weeks of life. In all developmental stage, the highest number of PC was observed in the duodenum of 13 days old guinea pigs. Our results confirm the presence of PC in the small intestine of guinea pigs from birth.

Pharmacokinetics of Intravesical Versus Oral Oxybutynin in Healthy Adults: Results of an Open Label, Randomized, Prospective Clinical Study

We investigated the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results. We performed an open label, randomized, 3-period crossover clinical study in 20 healthy adults. In periods 1 and 2 subjects received a single dose of 10 mg oxybutynin HCl solution intravesically or a 5 mg tablet orally. Period 3 comprised repeat intravesical applications (7 doses) of 10mg oxybutynin HCl. Enantioselective concentrations of oxybutynin and N-desethyloxybutynin were quantified by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods, analyzed by descriptive statistics and compared using the average bioequivalence approach. Systemic exposure to racemic oxybutynin after intravesical administration was significantly greater, yielding 294% (90% CI 211-408) of that after oral intake of immediate release preparations, as measured by the dose normalized area under the plasma concentration time curve. In contrast, systemic exposure to racemic N-desethyloxybutynin reached only 21% (90% CI 15-29). The area under the plasma concentration time curve ratio of N-desethyloxybutynin to oxybutynin was 14-fold decreased for intravesical administration. After intravesical multidose administration, the cumulation of oxybutynin (1.3-fold) and N-desethyloxybutynin (1.6-fold) was weak, absorption was prolonged and apparent elimination half-lives were longer. The study medication was well tolerated with a third of participants reporting anticholinergic adverse effects. Our study provides evidence of significantly higher bioavailability of intravesical vs oral administration of oxybutynin due to circumvention of the intestinal first pass metabolism. Given the high efficacy and decreased rate of adverse effects, intravesical oxybutynin should be considered in patients with neurogenic lower urinary tract dysfunction who do not tolerate oral administration or in whom oral preparations fail to improve detrusor overactivity.

Mast cell expression of the serotonin1Areceptor in guinea pig and human intestine

Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries. Mast cells in human and guinea pig preparations expressed the 5-HT1A receptor. ELISA detected spontaneous release of histamine in guinea pig and human preparations. The selective 5-HT1A receptor agonist 8-hydroxy-PIPAT evoked release of histamine. A selective 5-HT1A receptor antagonist, WAY-100135, suppressed stimulation of histamine release by 5-HT or 8-hydroxy-PIPAT. Mast cell-stabilizing drugs, doxantrazole and cromolyn sodium, suppressed the release of histamine evoked by 5-HT or 8-hydroxy-PIPAT in guinea pig and human preparations. Our results support the hypothesis that serotonergic degranulation of enteric mast cells and release of preformed mediators, including histamine, are mediated by the 5-HT1A serotonergic receptor. Association of 5-HT with the pathophysiology of functional gastrointestinal disorders (e.g., irritable bowel syndrome) underlies a question of whether selective 5-HT1A receptor antagonists might have therapeutic application in disorders of this nature.