Gastric Motility In Rats Research Articles

Effects of exogenous nesfatin-1 on gastric distention-sensitive neurons in the central nucleus of the amygdala and gastric motility in rats

Nesfatin-1 is a novel brain–gut peptide identified in several brain regions associated with feeding and gastrointestinal function. Our study explored the effects of nesfatin-1 in the central nucleus of the amygdala (CNA) on the activity of gastric distention (GD)-sensitive neurons, gastric motility, and the potential regulation mechanisms by the dorsal motor nucleus of the vagus (DMV). Following retrograde injection of fluorogold (FG) into the DMV, we found that nesfatin-1/FG dual-labeled neurons were detected in the CNA, which indicates that some of the nesfatin-1-immunoreactive neurons arising from the DMV may project to the CNA. Single unit discharges in the CNA were recorded extracellularly, and gastric motility was monitored by implantation of a force transducer into the stomach of conscious rats. These results showed that nesfatin-1 administration to the CNA excited most of the GD-excitatory neurons, inhibited GD-inhibitory neurons, and dose-dependently reduced gastric motility. All of the above effects induced by nesfatin-1 could be partially blocked by pretreatment with the melanocortin 3/4 receptors antagonist, SHU9119. Electrical stimulation of the DMV excited the majority of the nesfatin-1-responsive GD neurons in the CNA. Additionally, pretreatment with an anti-NUCB2/nesfatin-1 antibody in the CNA increased the firing rate of nesfatin-1-responsive GD-inhibitory neurons but decreased the firing rate in nesfatin-1-responsive GD-excitatory neurons following electrical stimulation of the DMV. Finally, a subdiaphragmatic vagotomy eliminated the diminished gastric motility induced by nesfatin-1 injection. Taken together, these findings suggest that nesfatin-1 regulates the activity of GD-sensitive neurons and gastric motility via the melanocortin pathway in the CNA. Furthermore, the DMV may be involved in this regulatory pathway.

Somatosensory Nerve Fibers Mediated Generation of De-qi in Manual Acupuncture and Local Moxibustion-Like Stimuli-Modulated Gastric Motility in Rats.

The aim of this study was to reveal the somatosensory nerve fibers mediated generation of De-qi in manual acupuncture stimuli (MAS) and local moxibustion-like stimuli (LMS). The effects of strong and slight MAS, as well as 41°C, 43°C, and 45°C LMS at ST36 and CV12 on gastric motility were observed in rats. Gastric motility was continuously measured by an intrapyloric balloon, and the average amplitude, integral, and frequency of gastric motility during LMS were compared with those of background activity. Gastric motility was facilitated by MAS and LMS at ST36 and inhibited at CV12. The modulatory effects induced by strong MA with potent De-qi (needle grasp feeling) were markedly higher than those by slight MA with mild De-qi sensation (P < 0.05). The nociceptive 43°C and 45°C LMS, rather than nonnociceptive 41°C LMS, produced significant regulatory effects on gastric motility. Based on the afferent fibers activated in the present study, these results support the hypothesis that Aδ- and C-afferent fibers were more likely to be involved in the generation of De-qi sensation.

Central nesfatin‐1 influences the excitability of ghrelin‐responsive gastric distension neurons in the arcuate nucleus and reduces gastric motility in rats

Although the novel satiety peptide nesfatin-1 has been shown to regulate gastric motility, the underlying mechanisms have yet to be elucidated. The study aimed to explore the effects of nesfatin-1 on ghrelin-responsive gastric distension (GD) neurons in the arcuate nucleus (Arc), and potential regulation mechanisms of gastric motility by the paraventricular nucleus (PVN). Single-unit discharges in the Arc were recorded extracellularly, and gastric motility in conscious rats was monitored during the administration of nesfatin-1 to the Arc or electrical stimulation of the PVN. Retrograde tracing and fluo-immunohistochemistry staining were used to determine NUCB2/nesfatin-1 neuronal projections. Nesfatin-1 inhibited most of the ghrelin-responsive GD-excitatory neurons, but excited ghrelin-responsive GD-inhibitory neurons in the Arc. Gastric motility was significantly reduced by nesfatin-1 administration to the Arc in a dose-dependent manner. The firing activity in the Arc and changes to gastric motility were partly reduced by SHU9119, an antagonist of melanocortin 3/4 receptors. Electrical stimulation of PVN excited most of the ghrelin-responsive GD neurons in the Arc and promoted gastric motility. Nonetheless, pretreatment with an anti-NUCB2/nesfatin-1 antibody in the Arc further increased the firing rate of most of the ghrelin-responsive GD-excitatory neurons and decreased the ghrelin-responsive GD-inhibitory neurons following electrical stimulation of the PVN. Gastric motility was enhanced by pretreatment with an anti-NUCB2/nesfatin-1 antibody in the Arc following PVN stimulation. Furthermore, NUCB2/nesfatin-1/fluorogold double-labeled neurons were detected in the PVN. These results suggest that nesfatin-1 could serve as an inhibitory factor in the Arc to regulate gastric motility via the melanocortin pathway. The PVN could be involved in the regulation of the Arc in gastric activity.

Alterations in TH- and ChAT-immunoreactive neurons in the DMV and gastric dysmotility in an LPS-induced PD rat model

To study movement disorder in Parkinson's disease (PD), an animal model of PD can be created by injecting lipopolysaccharide (LPS) into the substantia nigra of rats. In addition to body movement disorders, patients with PD often experience gastrointestinal (GI) dysfunction, such as gastroparesis. However, the underlying mechanism of these disorders remains unclear. The dorsal motor nucleus of vagus (DMV) is a well-known visceral nucleus that regulates GI function. The present study investigated alterations in DMV neurons and gastric motility in rats with LPS-induced PD (LPS-PD rats). Gastric motility was recorded using a strain gauge force transducer in vivo. The distributions of tyrosine hydroxylase (TH)- and choline acetyltransferase (ChAT)-positive neurons in the DMV were determined using immunofluorescence and confocal laser microscopy. Our results indicated that in LPS-PD rats, the number of neurons in the substantia nigra, including neurons with TH immunoreactivity, was markedly reduced, although glial cell proliferation was clearly observed. However, enhanced TH immunoreactivity and decreased ChAT immunoreactivity were found in the DMV. Furthermore, weakened gastric motility was recorded in anesthetized LPS-PD rats. In conclusion, rats with LPS-induced PD exhibited gastric dysmotility with an alteration in DMV neurons. This PD model may be used to study autonomic nervous system disorders that are often observed in patients with early-stage PD.

Central apelin contributes to stress‐induced impaired gastric motility in rats

Stress plays a major role in functional gastrointestinal (GI) disorders. GI symptoms may develop as a result of accumulation stressors in some individuals while others can adapt to stressors. Exposure to repeated experience with the same stressor can produce an adaptation of behavioral and hypothalamic‐pituitary‐adrenal (HPA) axis response. However, the adaptation mechanism remains unclear. Acute restraint stress (ARS) increases corticotrophin releasing factor (CRF) in hypothalamic paraventricular nucleus (PVN) leads delayed gastric emptying (GE) via autonomic neural pathways in rats. ARS‐induced delayed GE is completely restored following chronic single stress (CSS) while restoration is no longer observed following chronic complicated stress (CCS). Apelin is upregulated in PVN in response to stress. Central effects of apelinergic system are attributed to regulation of stress response. We performed GE measurement and brain microdialysis from PVN under non‐stressed, ARS, CSS and CCS conditions in rats. ARS significantly increased CRF and apelin concentrations. CSS attenuated this response, whilst concentrations remained significantly high following CCS. ARS delayed GE which was completely restored following CSS, but not CCS. Central administration of apelin antagonist F13A restored delayed GE following ARS and CCS. Thus, apelin may be a candidate for treatment of stress‐induced GI disorders.

“Intensity-Response” Effects of Electroacupuncture on Gastric Motility and Its Underlying Peripheral Neural Mechanism

The aim of this study was to explore the “intensity-response” relationship between EAS and the effect of gastric motility of rats and its underlying peripheral neural mechanism by employing ASIC3 knockout (ASIC3−/−), TRPV1 knockout (TRPV1−/−), and C57BL/6 mice. For adult male Sprague-Dawley (n = 18) rats, the intensities of EAS were 0.5, 1, 3, 5, 7, and 9 mA, respectively. For mice (n = 8 in each group), only 1 mA was used, by which C fiber of the mice can be activated. Gastric antrum motility was measured by intrapyloric balloon. Gastric motility was facilitated by EAS at ST36 and inhibited by EAS at CV12. The half maximal facilitation intensity of EAS at ST36 was 2.1–2.3 mA, and the half maximal inhibitory intensity of EAS at CV12 was 2.8 mA. In comparison with C57BL/6 mice, the facilitatory effect of ST36 and inhibitive effect of CV12 in ASIC3−/− mice decreased, but the difference was not statistically significant (P > 0.05). However, these effects in TRPV1−/− mice decreased significantly (P < 0.001). The results indicated that there existed an “intensity-response” relationship between EAS and the effect of gastric motility. TRPV1 receptor was involved in the regulation of gastric motility of EAS.

CGMP–PDE3–cAMP signal pathway involved in the inhibitory effect of CNP on gastric motility in rat

In the present study, we investigated the mechanism of C-type natriuretic peptide (CNP)-induced inhibitory effect on spontaneous contraction of gastric antral smooth muscle to clarify CNP-NPR-B/pGC-cGMP downstream signal transduction pathway using organ bath and ELISA methods in rat. CNP significantly reduced the amplitude of the spontaneous contraction and increased the contents of cGMP and cAMP in the gastric antral smooth muscle tissue. In the presence of IBMX, a non-selective phosphodiesterase (PDE) inhibitor, the inhibitory effect of CNP on spontaneous contraction was significantly suppressed; however, the production of cGMP but not cAMP was still increased by CNP. EHNA, a PDE2 inhibitor, did not affect both CNP-induced inhibition of the contraction and CNP-induced increase of cGMP and cAMP generations in gastric smooth muscle tissue, while milrinone, a PDE3 inhibitor, similar to IBMX, attenuated the CNP-induced inhibitory effect on spontaneous contraction and increased the content of cGMP but not cAMP. The results suggest that cGMP–PDE3–cAMP signal pathway is also involved in the CNP-induced inhibition of gastric motility in rat.

Regulative Roles of Ghrelin in Ingestive Behavior, Upper Gastrointestinal Motility, and Secretion

Ghrelin was recently identified as the first endogenous ligand for growth hormone secretagogue receptors (previously known as orphan receptors). Two major molecular forms of ghrelin are found in the stomach and plasma: acyl ghrelin with O-n-octanoylated serine at position 3 and des-acyl ghrelin. Interestingly, these distinct molecular forms play contrasting roles in ingestive behavior, upper gastrointestinal motility, and gastric acid secretion. Acyl ghrelin stimulates food intake both in fed and fasted rodents and induces adiposity, alleviates ingestive behavior, stimulates gastrointestinal motor activity and gastric acid secretion, and accelerates gastric emptying in several species. In contrast, des-acyl ghrelin has been demonstrated to disrupt gastric motility in rats and delay gastric emptying in mice and rats. Thus, acyl ghrelin is a potent stimulator of ingestive behavior, gastrointestinal motility, and gastric acid secretion, whereas des-acyl ghrelin exerts opposing effects on ingestive behavior and gastrointestinal motility but does not affect gastric acid secretion. Ghrelin is expected to be used in various applications such as therapeutic strategies for obesity, anorexia, cachexia, and cardiovascular disease in the clinical setting. In this article, we review the evidence on the roles of acyl ghrelin and des-acyl ghrelin in the regulation of ingestive behavior, upper gastrointestinal motility, and gastric acid secretion in mammals; moreover, we mention the effects of ghrelin on oral functions.

Lead exposure changes gastric motility in rats: role of nitric oxide (NO).

Abdominal colic, constipation and delay in gastric emptying are symptoms of lead poisoning, but there is scant information about the effect of lead on gastric motility. In the present study, we investigated the effect of lead acetate on gastric motility in rats. Animals were divided into nine groups (n=8); four groups were exposed to lead acetate solution (1%) for 1, 2, 3, and 4 weeks (Pb1, Pb2, Pb3, and Pb4 groups, respectively). Sodium acetate solution was given to another four groups for 1, 2, 3, and 4 weeks (Na1, Na2, Na3, and Na4 groups, respectively) and the control group had free access to tap water. Gastric motility was measured in the basal and acetylcholine (Ach)-stimulated states using a physiograph instrument. Nitric oxide metabolite of gastric tissue was determined by Griess micro-assay. There were no significant differences between basal and Ach-stimulated gastric motility in Pb1, Pb2, Na1, and Na2 groups. However, it was significantly greater in Pb3 and Pb4 groups when compared with Na3 and Na4 groups in both basal and Ach-stimulated states (P<0.05). In addition, nitric oxide metabolite of gastric tissue was more in all Pb groups in comparison with their Na counterparts (P<0.05). We found that lead exposure could affect gastric motility via the nitric oxide pathway.

Effect of motilin on gastric distension sensitive neurons in arcuate nucleus and gastric motility in rat

Intestinal motilin is known to stimulate gastrointestinal (GI) motility and the arcuate nucleus (Arc) of hypothalamus is shown to be involved in the regulation of GI motility. Single unit discharges in the Arc were recorded extracellularly by implantation of a force transducer into the stomach in rats, to evaluate the effect of motilin on gastric motility. Projection of nerve fiber and expression of motilin were observed by retrograde tracer deposits of Fluoro-Gold (FG) and fluo-immunohistochemistry staining. 65.5% of neurons in Arc responded to gastric distension (GD), 55.6% of which showed excitation (GD-E), and 44.4% showed inhibition (GD-I). After GD, the firing rate of GD-E neurons significantly increased (P<0.01), but decreased for GD-I neurons (P<0.01). Most of both GD-E and GD-I neurons were activated by motilin (P<0.05). The frequency and amplitude of gastric contractions significantly increased by administration of motilin in Arc with a dose dependent manner (P<0.05-0.01). However, pretreatment with GM109 could abolish the responses of neurons and excitatory effect of gastric motility induced by motilin. Motilin immunoreactive neurons were increased in Arc via gastric distention (P<0.05). Motilin/FG-labeled neurons were detected in hypothalamus paraventricular nucleus (PVN). Our findings suggest that motilin neurons in Arc may accept peripheral somatosensory afferent inputs from gastric mechanoreceptors of the stomach, and also may acts as a stimulatory factor in Arc to regulate gastric motility via some inferior nucleus relay pathway. The results provide insight into the role of Arc in the control of digestion mediated via motilin.

The possible involvement of dopamine D 3 receptors in the regulation of gastric emptying in rats

Aim The inhibitory effect of dopamine on gastric motility is thought to be mediated via a decrease in acetylcholine release resulting from stimulation of enteric neuronal dopamine D 2 receptors. The aim of this study was to investigate the possible involvement of the dopamine D 3 receptor in the regulation of gastric motility in rats using selective dopamine D 3 receptor agonists or a dopamine D 3 receptor antagonist. Main methods Gastric emptying was assessed using the phenol red method after rats were treated with varying doses of dopamine D 3 receptor agonists or a dopamine D 3 receptor antagonist. Key findings S(+)-PD 128,907 (0.01–1 mg/kg, s.c.), a selective dopamine D 3 receptor agonist, dose-dependently delayed gastric emptying in rats. Other dopamine D 3 receptor agonists (i.e., R(+)-7-OH-DPAT [0.03–1 mg/kg, s.c.] and quinpirole [0.01–1 mg/kg, s.c.]) also delayed gastric emptying in rats. Both the selective dopamine D 1 and D 5 receptor agonist SKF-38393 and the selective dopamine D 4 receptor agonist PD 168,077 failed to delay gastric emptying in rats. The selective dopamine D 3 receptor antagonist (+)-S 14297 (10 mg/kg, s.c.) partially inhibited the S(+)-PD 128,907-induced delay in gastric emptying. Although an administration of S(+)-PD 128,907 (1–100 μg/kg) into the 4th cerebral ventricle partially and dose-dependently delayed gastric emptying in rats, its administration into the lateral cerebral ventricle did not affect gastric emptying. Significance The results presented here suggest that peripheral dopamine D 2 receptors and, at least in part, dopamine D 3 and central dopamine D 2/D 3 receptors play an important role in the regulation of gastric motility in rats.

TLQP-21, a VGF-Derived Peptide, Prevents Ethanol-Induced Gastric Lesions: Insights into Its Mode of Action

Background and Aim: TLQP-21, a peptide derived from the vgf gene, has been reported to play a role in the regulation of rat gastric motility, but its influence on gastric mucosal integrity is unknown. Experimental Approach: We investigated the effects of central (0.8–8 nmol/rat) or peripheral (48–240 nmol/kg) TLQP-21 administration on ethanol- (EtOH, 50%, 1 ml/rat) induced gastric lesions in the rat. The mechanisms involved in such activity were also examined. Results: Central TLQP-21 injection dose-dependently reduced EtOH-induced gastric lesions (ED₅₀ = 3.16 nmol), while peripheral TLQP-21 administration had no effect. The TLQP-21 gastroprotective effect against EtOH injury was accompanied by a significant increase in gastric prostaglandin E₂ (PGE₂) production linked to an increase in constitutive cyclooxygenase (COX) expression. The nitric oxide (NO) synthase inhibitor L-NAME (70 mg/kg, s.c.), the nonselective COX inhibitor indomethacin (10 mg/kg, orally) and capsaicin denervation removed TLQP-21 gastroprotection. Conclusions: This study shows for the first time that central TLQP-21 exerts a protective action on the gastric mucosa exposed to the noxious agent EtOH. TLQP-21 gastroprotection is mediated by constitutive-derived NO and PGE₂, and requires the integrity of sensory nerve fibers.

Central orexin-A increases gastric motility in rats

Orexin receptor type-1 (OX1R) is expressed in the dorsal motor nucleus of vagi (DMV). Although orexin-A (OXA) plays an important role in mediating stress responses, it remains unclear how central OXA regulates gastric dysmotility induced by stress. Acute restraint stress (ARS) delays solid gastric emptying via the central corticotropin releasing factor (CRF) and peripheral autonomic neural pathways. We have previously shown that ARS impairs postprandial antro-pyloric coordination and delays solid gastric emptying in rats. We also showed that postprandial gastric contractions were augmented in response to ARS in rats. However, the mechanism of augmented postprandial gastric contractions induced by ARS remains unclear. We tested the hypothesis that augmented gastric motility induced by ARS is mediated via the central OX1R. We also assessed the role of endogenous OXA in the mediation of gastric motility under non-stressed conditions in conscious rats. A strain gauge transducer was implanted on the antrum to record postprandial gastric motility. To investigate whether endogenous OXA is involved in ARS-induced augmented gastric motility, selective OX1R antagonist, SB-334867 (16 μg), was administered intracerebroventricularly (icv). Icv-injection of SB-334867 abolished the augmented gastric contractions induced by ARS. Spontaneous postprandial gastric motility was enhanced by icv-injection of OXA (10 μg), while it was attenuated by icv-injection of SB-3334867. It is suggested that central OXA mediates augmented gastric motility induced by ARS in rats. Central OXA also modulates postprandial gastric contractions in non-stressed conditions.

Ghrelin stimulates gastric motility of the guinea pig through activation of a capsaicin-sensitive neural pathway:in vivoandin vitrofunctional studies

Ghrelin stimulates gastric motility in rats, mice and humans. Although ghrelin and the ghrelin receptor are known to be expressed in the guinea-pig gastrointestinal tract, the effects of ghrelin on gastric motility have not been examined. Aim of the present study was to clarify the motor-stimulating action of ghrelin in the guinea-pig stomach. Gastric motility was measured as intraluminal pressure changes using a balloon inserted in the stomach of urethane-anaesthetized guinea pigs. The effects of ghrelin on gastric muscle contraction and [(3)H]-efflux from [(3)H]-choline-loaded strips were investigated in vitro. Ghrelin (0.3-30 microg kg(-1), i.v.) increased gastric motility in a dose-dependent manner but des-acyl ghrelin was ineffective. The action of ghrelin was completely inhibited by hexamethonium and D-Lys(3)-growth-hormone releasing peptide-6. Atropine partially decreased the stimulatory action of ghrelin. In capsaicin-pretreated guinea pigs, the ghrelin-induced response was markedly decreased. Ghrelin (1 micromol L(-1)) did not affect [(3)H]-efflux in non-stimulated preparations but significantly decreased electrical field stimulation (EFS)-induced [(3)H]-efflux. L-Nitro arginine methylester (L-NAME) attenuated the inhibition of [(3)H]-efflux by ghrelin. Ghrelin did not cause any mechanical changes in gastric strips. Electrical field stimulation caused relaxation of gastric strips, which changed to atropine-sensitive contraction in the presence of L-NAME. Relaxation induced by EFS was slightly potentiated, but the EFS-induced contraction was not affected by ghrelin. Ghrelin stimulates gastric motility of the guinea pig through activation of capsaicin-sensitive vago-vagal reflex pathway including efferent cholinergic neurons. Peripheral ghrelin receptors on enteric nitrergic nerves might affect the ghrelin-induced gastric action by releasing nitric oxide.

V 1 receptor in ENS mediates the excitatory effect of vasopressin on circular muscle strips of gastric body in vitro in rats

The purpose of this study was to localize vasopressin (VP) V 1a receptor in stomach and to characterize the role of VP in the regulation of gastric motility in rats. Double staining was used to locate the V 1a receptor in the gastric body of the rat. The contraction of the circular muscle strips of gastric body was monitored by a polygraph. V 1a receptor was expressed on the neurons of myenteric plexus of the gastric body. VP (10 − 10 –10 − 6 M) caused a concentration-dependent contractile effect on the circular muscle strips of gastric body in vitro. V-1880 ([deamino-Pen 1, O-Me-Tyr 2, Arg 8]-Vasopressin, 10 − 7 M), a V 1 receptor antagonist, inhibited the spontaneous contraction of the strips. Tetradotoxin (TTX, 10 − 6 M) and V-1880 (10 − 7 M) abolished the excitatory effect of VP. Atropine (10 − 6 M) partially inhibited VP-induced excitatory effect on the muscle strips but hexamethonium (10 − 4 M) did not influence it. These results suggest that V 1a receptor was expressed on the neurons of myenteric nerves. The cholinergic nerve was involved in the excitatory effect of VP on the contraction of gastric body.

Oxytocin receptor expressed on the smooth muscle mediates the excitatory effect of oxytocin on gastric motility in rats

The aim of this study was to localize oxytocin receptor (OTR) in the stomach and to investigate the effect of OT on gastric motility in rats. Western blot and immunohistochemistry methods were used to localize OTR in stomach. The motility of stomach was recorded in vivo (recording of the intragastric pressure), in vitro (recording of the contraction of muscle strips) and on isolated smooth muscle cells. OTR was expressed on cells of both circular and longitudinal muscle of stomach. Systemic administration of OT induced an early transient decrease and a subsequent increase on intragastric pressure. Devazepide (1 mg kg(-1), i.v.), a cholecystokinin-1 (CCK(1)) receptor antagonist, completely abolished the transient response but did not influence the subsequent one. OT (10(-9)-10(-6) mol L(-1)) dose-dependently increased the contraction of the muscle strips of gastric body, antrum, and pyloric sphincter, and decreased the average cell length of isolated smooth muscle cells. Tetrodotoxin and atropine did not influence the effect of OT on muscle strips. Pretreatment with atosiban, an OTR antagonist, inhibited the spontaneous contraction of muscle strips and abolished the excitatory effect of OT on the muscle strips and the isolated cells. These results suggest that the OTR is expressed on the smooth muscle of the stomach and mediates excitatory effect of OT on gastric motility.

Effects of repeated restraint stress on gastric motility in rats

In our daily life, individuals encounter with various types of stress. Accumulation of daily life stress (chronic stress) often causes gastrointestinal symptoms and functional gastrointestinal diseases. Although some can adapt toward chronic stress, the adaptation mechanism against chronic stress remains unknown. Although acute stress delays gastric emptying and alters upper gastrointestinal motility, effects of chronic stress on gastric motility still remain unclear. We investigated the effects of acute (single stress) and chronic (repeated stress for 5 consecutive days) stress on solid gastric emptying and interdigestive gastroduodenal contractions in rats. It is well established that acute restraint stress inhibits solid gastric emptying via central corticotropin-releasing factor (CRF). To investigate whether the sensitivity to CRF is altered following chronic stress, CRF was administered intracisternally. Ghrelin is involved in regulating gastric emptying and upper gastrointestinal motility in rodents. The changes in plasma active ghrelin levels and mRNA expression in the stomach were studied following chronic stress. To evaluate the effects of chronic stress on the hypothalamus-pituitary-adrenal (HPA) axis, plasma corticosterone levels were also measured. Delayed gastric emptying observed in acute stress was completely restored following chronic stress. Acute stress abolished gastric phase III-like contractions, without affecting duodenal phase III-like contractions in the interdigestive state. Impaired gastric phase III-like contractions were also restored following chronic stress. Plasma ghrelin levels and ghrelin mRNA expression were increased significantly after chronic stress. Intracisternal injection of CRF delayed gastric emptying and impaired gastric motility in rats who received chronic stress. Plasma corticosterone concentrations were no more elevated following chronic stress. The restored gastric emptying following chronic stress was antagonized by the administration of ghrelin receptor antagonists. The adaptation mechanism may involve upregulation of ghrelin expression and attenuation of the HPA axis. In contrast, the sensitivity to central CRF remained unaltered following chronic stress in rats.

Hindbrain Effects of L-Glutamate on Gastric Motility in Rats.

BackgroundThere are no unanimous standpoints about the dorsal motor nucleus of the vagus (DMV) and nucleus of solitary tract (NTS) involving in the regulation of gastric motility up to now.MethodsIn this study, we injected L-Glutamate (L-Glu), an incitant neurotransmitter in the central neural system, into DMV and NTS to further investigate the effects of the two nuclei on gastric motility. A latex balloon connected with a pressure transducer was inserted into the pylorus through the fundus for continuous recording of the change of gastric smooth muscle contractile curves.ResultsL-Glu (10 nmol in 0.1 µl) microinjected into right DMV and NTS significantly inhibited gastric motility. We compared the effects of L-Glu (10 nmol) microinjected into the two nuclei, the L-Glu microinjected into right NTS had the greater inhibitory effect on gastric motility than microinjected into the right DMV. The physiological saline microinjection evoked no significant effect on gastric motility.ConclusionsL-Glu microinjected into right DMV and NTS evoked significant inhibition on gastric motility in rats. At equal dose of L-Glu, NTS had the greater inhibitory effect than DMV.

Regulation of Ingestive Behavior, the Upper Gastrointestinal Motility and Gastric Acid Secretion by Ghrelin in Mammals

Ghrelin, a novel 28-amino acid peptide, was recently identified as the first endogenous ligand for growthhormone secretagogue receptors (previously known as orphan receptors), and discovered by “reverse pharmacology”. The ghrelin peptide features a unique post-translational modification of O-n-octanoylation at serine 3, and is secreted from X/A cells in gastric oxyntic glands into the blood circulation. Two major molecular forms of ghrelin are found in the stomach and plasma: acyl ghrelin with O-n-octanoylated serine in the position 3, and des-acyl ghrelin. Among dozens of enzymes, hormones and other factors secreted by the gastrointestinal tract in response to food in the lumen, acyl ghrelin is the only gastrointestinal signal to increase meal size. Acyl ghrelin stimulates food intake both in free-feeding (naturally fed) and food-deprived (fasted) rodents, and induces adiposity. Also, acyl ghrelin ameliorates cancer cachexia in nude mice, and alleviates ingestive behavior induced by cancer chemotherapy-related dyspepsia in normal rats. However, des-acyl ghrelin counteracts the metabolic but not the neuroendocrine response to acyl ghrelin. Transgenic mice overexpressing des-acyl ghrelin have been shown small phenotype. In addition, des-acyl ghrelin inhibits food intake in food-deprived mice and rats. Acyl ghrelin stimulates gastrointestinal motor activity and accelerates gastric emptying in rats, but not in dogs. On the contrary, des-acyl ghrelin has been shown to disrupt gastric motility in rats, and delay gastric emptying in mice and rats. For the majority of experiments, acyl ghrelin stimulates gastric acid secretion in rats, however, different results exist.

Inhibitory effect of the herbal antidepressant St. John’s wort (Hypericum perforatum) on rat gastric motility

St. John's wort (Hypericum perforatum) is a highly popular and effective herbal antidepressant that clinically interacts with a number of conventional drugs. Because alterations in gastric emptying can cause pharmacokinetic interactions, in the present study we evaluated the effect of a standardized extract prepared from the flowering tops of Hypericum perforatum (SJW extract) on rat gastric motility. Orally administered SJW extract delayed gastric emptying in vivo. In vitro studies showed that SJW extract was significantly more active in inhibiting acetylcholine (or prostaglandin E2)-induced contractions than electrical field stimulation (EFS)-induced contractions. The effect of SJW extract on EFS-induced contractions was unaffected by drugs that inhibit intrinsic inhibitory nerves or by tachykinin antagonists, but it was reduced by the 5-hydroxytryptamine antagonist methysergide. The inhibitory effect of SJW extract on acetylcholine-induced contractions was reduced by the sarcoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid, but not by the L-type Ca2+ channel blocker nifedipine or by methysergide. Among the chemical constituents of SJW extract tested, hyperforin and, to a lesser extent, the flavonoids kaempferol and quercitrin, inhibited acetylcholine-induced contractions. It is concluded that SJW has a direct inhibitory effect on smooth muscle and could also possibly modulate gastric neurotransmission. If extended to humans, the inhibitory effect of SJW extract on gastric emptying in vivo could contribute, at least in part, to the clinical pharmacokinetic interactions between conventional medicines and this herbal antidepressant.