Inhibition of antral and pyloric electrical activity by vagal afferent stimulation in the rabbit

The effects of stimulation of cervical vagal afferents on the electromyographic activity (e.m.g.) of the gastric antrum and pylorus have been studied both in conscious and decorticate, curarized rabbits. In the latter group, stimulation at 10-15 Hz (0.3-0.4 mA; 5-7 ms duration) inhibited both the antral and pyloric e.m.g. in 21 rabbits, elicited an excitatory response in two more but produced no change in the remaining 13 animals. The inhibitory response was not affected by guanethidine (1 mg/kg, i.v.), phentolamine (1 mg/kg, i.v.) or propranolol (0.1 mg/kg, i.v.) and persisted in rabbits in which the contralateral cervical vagus and both splanchnic nerves had been cut, the coeliac ganglia and both adrenal glands had been extirpated. It was only abolished by combined section of the spinal cord at the level of C1, C2 and the contralateral vagus in the neck. In conscious rabbits, vagal stimulation at 2-5 Hz (0.4 mA; 0.5-1.0 ms duration) consistently inhibited antral and pyloric e.m.g. This inhibitory response persisted in the presence of phentolamine, propranolol and naloxone (0.25-1.00 mg/kg), and in adrenalectomized rabbits with cut splanchnic nerves and extirpated coeliac ganglia. However, it was completely abolished by section of both vagi above the diaphragm. It is concluded that (1) the vagal afferents responsible for the inhibition of the gastric e.m.g. are already included in the abdominal vagus nerves, (2) this inhibition of gastric e.m.g. is mediated by non-adrenergic fibers, one group of them emerging from the thoracic spinal cord to join the thoracic vagi via the stellate ganglia.     

Central effect of mu-opioid agonists on antral motility in conscious rats

Centrally applied opioids delay gastric emptying and inhibit intestinal transit. However, the mechanism of inhibitory effects of central opioids on gastric motility still remains unclear. It also remains unclear which opioid receptor (mu, delta, and kappa) stimulation affects gastric motility. We studied the central effect of opioids on antral motility in conscious rats. A strain gauge transducer was implanted on the gastric antrum to record the circular muscle contractions. The area under the curve of the antral motility, calculated as a motility index, was evaluated before and after the intracerebroventricular (icv) injection of various opioid agonists in each rat. [D-Ala2, N-Me-Phe4, Gly5-ol] enkephalin (DAMGO, 0.1-10 nmol), a mu-opioid selective agonist, significantly inhibited antral motility in a dose-dependent manner (n=4). The motility index was significantly decreased to 47.3+/-10.8% (n=4) of controls at 20 min after icv injection of DAMGO (1.0 nmol). In contrast, [D-pen2, L-Pen5] enkephalin (DADLE, 1.0 nmol), a delta-opioid selective agonist, and U50,488 (1.0 nmol), a kappa-opioid selective agonist, had no significant effects on antral motility. Pretreatment with subcutaneous guanethidine (5 mg/kg) and propranolol (1 mg/kg), but not phentolamine (1 mg/kg), significantly antagonized the inhibitory effect of DAMGO (1.0 nmol). Reduced motility index induced by DAMGO (1.0 nmol) was restored from 48.7+/-3.5% to 88.6+/-10.9% (n=5) and 80.4+/-2.2% (n=5) by guanethidine and propranolol, respectively. Our findings suggest that central mu-opioid receptor has major inhibitory effects on antral motility in conscious rats. The inhibitory effects of mu-opioid receptors are mediated via sympathetic pathways and beta-adrenoceptors.     

Differential effects of motilin on interdigestive motility of the human gastric antrum, pylorus, small intestine and gallbladder

Motilin was infused in this study with the aim of examining refractory characteristics for motilin stimulation of antral phase III and fasting gallbladder emptying. Moreover, interdigestive pyloric and small intestinal motility from duodenum to ileum were studied, as these may be target organs for motilin. Eight fasting, healthy male volunteers received, on separate subsequent days, repeated infusions of 13leucine-motilin (8 pmol (kg min)(-1) for 5 min) or saline at 30 min after phase IIIs in the duodenum. Interdigestive motility of the antrum, pylorus, duodenum, jejunum and ileum was measured for maximum 10 h by using a 21-lumen perfused catheter. Gallbladder motility was measured by ultrasonography. Motilin infusions induced antral phase IIIs, but only after a preceding phase III of duodenal origin. Under this condition, time-interval to phase III at the duodenal recording site was 30 +/- 13 (SEM) min after motilin, compared with 79 +/- 14 min after saline (P < 0.01), and compared with 121 +/- 13 min for motilin infusion following an antral phase III (P < 0.001). Motilin did not affect small intestinal motility or isolated pyloric pressure waves (IPPWs). However, the number of IPPWs was significantly affected by the origin of the preceding phase III, irrespective of whether motilin or saline was infused. Gallbladder volume decreased significantly within 10 min after each motilin infusion. We conclude that this study clearly demonstrates differential regional effects of motilin. Motilin initiates antral phase IIIs, but stimulation is subject to a refractory period which is clearly prolonged after a preceding antral phase III. Motilin induced gallbladder emptying, however, is not subject to a refractory state. Small intestinal phase IIIs as well as pyloric IPPWs are not affected by motilin.     

Sympatho-inhibitory baroreflex in conscious rabbits: simultaneous recordings of sympathetic and aortic nerve activity

The purpose of this study was to evaluate simultaneously the activity of afferent and efferent neuronal pathways of the sympatho-inhibitory baroreceptor reflex in conscious rabbits. Bipolar electrodes were implanted around the intact aortic nerve and cervical sympathetic trunk. Baroreceptor activity and sympathetic discharges were continuously recorded along with mean blood pressure. The baroreceptor reflex response was evoked by changes in mean arterial pressure induced by i.v. administration of phenylephrine 10 micrograms/kg and sodium nitroprusside 10 micrograms/kg. The baroreflex was analysed as parallel changes of afferent and efferent activities per mmHg of mean blood pressure rise or fall. This method of investigation of baroreflex responsiveness permits analysis of afferent and efferent neural activities under different behavioural conditions in conscious animals.     

Renal sympathetic responses to changes in arterial pressure in conscious rabbits

Renal sympathetic nerve activity (RSNA) at rest and in response to changes in mean arterial pressure (MAP) were examined by measuring norepinephrine (NE) spillover rate across the kidney in 14 conscious rabbits. NE spillover rate was calculated from veno-arterial difference in plasma NE concentrations across the kidney corrected by the fractional extraction of infused tritiated NE. Renal NE spillover rate (mean +/- S.E.M.) at rest in 14 conscious rabbits was 14.7 +/- 0.9 ng/min. During sodium nitroprusside infusions at 10 and 20 micrograms/kg/min, renal NE spillover rate significantly increased by 55 and 101% in response to falls in MAP of 15 and 19% respectively. During phenylephrine infusion at 2 micrograms/kg/min, renal NE spillover rate significantly decreased by 40% in response to a 14% rise in MAP. The relative contribution of renal to total NE spillover rate decreased during sympathetic stimulation, while this ratio was unchanged during sympathetic inhibition. This study demonstrates that the renal NE spillover method is sufficiently sensitive and reliable to detect the responses in RSNA to physiological stimuli in conscious rabbits. The difference observed in the degree of stimulation of renal versus total NE spillover rate during hypotension produces confirmation that sympathetic responses are not uniformly distributed in the body.     

The role of vasoactive intestinal polypeptide in the inhibition of antral and pyloric electrical activity in rabbits

The nature of the neurotransmitter released by intramural non-cholinergic non-adrenergic inhibitory neurones and the type of vagal afferents involved in the inhibition of antral and pyloric electrical activity induced by vagal afferent stimulation were investigated in conscious rabbits in which both splanchnic nerves had previously been cut. The inhibitory effect of duodenal distension was reversed by bilateral thoracic vagotomy. Either intravenous or intra-aortic infusions of vasoactive intestinal polypeptide (VIP) inhibited the electrical activity of both antrum and pylorus for several minutes. Electrical stimulation of afferent vagal fibres and duodenal distension both inhibited antral and pyloric activity and produced a significant increase of portal plasma VIP concentration. Numerous VIP-immunoreactive fibres were found to be present in the muscular layers of the pylorus. The possibility that this form of inhibition is mediated by VIPergic fibres is discussed as is the likely involvement of vagal afferent fibres in the case of the response to duodenal distension.     

Hyperglycemia impairs antro-pyloric coordination and delays gastric emptying in conscious rats

Delayed gastric emptying has been shown in diabetes. Although it has been proposed that hyperglycemia, and not only autonomic neuropathy, contributes to the pathogenesis of delayed gastric emptying, the inhibitory mechanism of hyperglycemia on gastric emptying remains unclear. We studied the effects of hyperglycemia per se on gastric emptying and postprandial gastric motility in conscious rats. Liquid and solid gastric emptying were compared between saline-infused rats and D-glucose-infused rats. Two strain gauge transducers were implanted on the antrum and pylorus and the postprandial antro-pyloric coordination was compared between euglycemia and hyperglycemia. D-glucose infusion for 30 min increased blood glucose level from 5.4 +/- 0.5 to 13.0 +/- 1.3 mM and significantly delayed gastric emptying. Forty minutes after the feeding, contractions with low frequency (<3 cycles min(-1)) and high amplitude (>15 g) of the antrum were observed. This period reflects the emptying process of the gastric content and the coordination between the antrum and pylorus was frequently observed. D-glucose infusion significantly reduced feeding-induced antral contractions and abolished the number of episodes of antro-pyloric coordination. Sham feeding-induced gastric contractions were also significantly reduced by hyperglycemia. Postprandial antro-pyloric coordination was not observed in vagotomized rats, suggesting a mediation of vagus nerve. It is concluded that hyperglycemia impairs antral contractions and antro-pyloric coordination in rats. The inhibitory effect of hyperglycemia on gastric emptying is mediated, at least in part, via impaired vagal activity.     

Spinal 5-HT2A receptors regulate cutaneous sympathetic vasomotor outflow in rabbits and rats; relevance for cutaneous vasoconstriction elicited by MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") and its reversal by clozapine

We determined whether spinal 5-hydroxytryptamine 2A (5-HT2A) receptors contribute to resting cutaneous sympathetic vasomotor activity, and to increases in activity elicited by electrical stimulation of the medullary raphe/parapyramidal region, and whether these receptors are involved in the cutaneous vasoconstricting action of systemically administered MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") and its reversal by clozapine. Experiments were conducted in urethane-anesthetized rabbits and rats. Administration of the 5-HT2A antagonist, trans-4-((3Z)3-[(2-Dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate (SR 46349B, 0.1 mg/kg, i.v.) inhibited resting ear pinna sympathetic vasomotor nerve discharge and reduced the extent to which raphe/parapyramidal electrical stimulation caused ear pinna (rabbit) and tail (rat) artery blood flow to fall. Clozapine (0.125-0.5 mg/kg, i.v.) also reduced the fall in ear pinna blood flow elicited by raphe/parapyramidal stimulation. In rabbits, after inactivation of raphe/parapyramidal function by local microinjection of muscimol (1 nmol in 100 nl), the 5-HT2A agonist R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI, 50 microg/kg, i.v.) increased ear pinna sympathetic nerve activity from 3+/-2% to 129+/-5% of pre-muscimol levels (P<0.01, n=6), and this increase was abolished by section of the ipsilateral cervical sympathetic nerve trunk. MDMA (2 mg/kg, i.v.) after muscimol decreased ear pinna blood flow from 33+/-10 to 2+/-1 cm/s (P<0.01, n=5) and increased ear pinna sympathetic nerve activity from 8+/-4% to 120+/-41% of pre-muscimol levels (P<0.01, n=6). The MDMA-elicited increase in nerve activity was abolished by SR 46349B. Data suggest that spinal 5-HT2A receptors contribute to sympathetically induced cutaneous vasoconstriction regulated by raphe/parapyramidal neurons in the brainstem, and that these receptors contribute to the cutaneous vasoconstricting action of MDMA and its reversal by clozapine.     

Loxiglumide abolishes the effects of intraduodenal oleic acid on gastric motility and emptying in the pig

Abstract The role of cholecystokinin in mediating the effects of intraduodenal fat infusion on gastric motility and gastric emptying and the pattern of transpyloric flow was evaluated in conscious pigs. Concurrent measurements of antropyloroduodenal motility with an eight-channel sleeve/sidehole catheter, transpyloric flow and gastric emptying after instillation of 1000 ml of saline into the stomach, were made during intraduodenal infusion of either normal saline or oleic acid at 5 ml min⁻¹. Studies with intraduodenal oleic acid were performed with and without intravenous infusion of loxiglumide (30 mg kg⁻¹ intravenous bolus 15 min before intraduodenal oleic acid, followed by intravenous infusion of 10 mg kg⁻¹ h⁻¹), Intraduodenal oleic acid was associated with stimulation of isolated pyloric pressure waves (P < 0.05), inhibition of antral pressure waves (P < 0.05), reduced pulsatile transpyloric flow (P < 0.05) and retardation of gastric emptying (P < 0.05). when compared to intraduodenal saline. Loxiglumide prevented retardation of gastric emptying by intraduodenal oleic acid (P < 0.05), and maintained it at values that were not significantly different from saline. After loxiglumide there were more antral pressure waves (P < 0.05) and less isolated pyloric pressure waves (P < 0.05) when compared to oleic acid.
These results indicate that the effects of intraduodenal oleic acid on gastric and pyloric motility, and gastric emptying are largely mediated by CCK-dependent mechanisms.     

Inhibitory neural pathway regulating gastric emptying in rats

The relaxation of the pylorus is one of the most important factors for promoting gastric emptying. However, the role of inhibitory neurotransmitters in the regulation of pyloric relaxation and gastric emptying remains unclear. In this study, we investigated the effects of NO biosynthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), and calcium dependent potassium channel blocker, apamin, on vagal stimulation-induced pyloric relaxation and gastric emptying in rats. Sodium nitroprusside (SNP), adenosine 5'-triphosphate (ATP), vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) caused pyloric relaxations in a dose dependent manner in vivo. Apamin (120 microg/kg) significantly reduced ATP and PACAP-induced pyloric relaxations without affecting SNP- or VIP-induced relaxations. Vagal stimulation (10 V, 1 ms, 1-20 Hz)-induced pyloric relaxation was significantly inhibited by L-NAME (10 mg/kg). The combined administration of L-NAME and apamin almost completely abolished vagal stimulation-induced pyloric relaxation. L-NAME and apamin significantly increased spontaneous contractions in the antrum, pylorus and duodenum. Increased motility index by L-NAME and apamin was significantly higher in the pylorus and duodenum, compared to that of antrum. L-NAME and apamin significantly delayed liquid gastric emptying. These results suggest that besides NO, probably ATP and PACAP, act as inhibitory neurotransmitters in the rat pylorus and regulate gastric emptying.     

Inhibition of gastric motility by noxious chemical stimulation of interspinous tissues in the rat

In urethane anesthetized, adult male Wistar rats, noxious chemical stimulation of the mid to lower thoracic interspinous tissues, in the form of capsaicin injection, was accompanied by a pronounced increase in gastric sympathetic nerve activity and inhibition of gastric motility. Much weaker effects on gastric sympathetic nerve activity and gastric motility were observed with similar stimulation of the lower lumbar interspinous tissues. The inhibitory response of gastric motility to thoracic stimulation was preserved in spinalized animals, somewhat diminished in vagotomized animals and was abolished in most animals from which the coeliac ganglion had been extirpated. In vagotomized animals, treatment with 1 mg/kg propranolol i.v. did not cause any further attenuation of the inhibitory reflex. However, the inhibitory reflex was extinguished in vagotomized animals which received 1 mg/kg propranolol plus 10 mg/kg phentolamine i.v. These results suggest that noxious chemical stimulation of the interspinous tissues elicits a segmentally organized reflex which is mediated principally at the spinal level and which expresses itself principally, but not exclusively via sympathetic efferents traversing the coeliac ganglion. The expression of the reflex response appears to be largely dependent upon the integrity of alpha adrenergic receptors.     

Acotiamide, a new orally active acetylcholinesterase inhibitor, stimulates gastrointestinal motor activity in conscious dogs

Background Acotiamide hydrochloride (acotiamide), a novel selective acetylcholinesterase (AChE) inhibitor, has proven significantly effective in treating functional dyspepsia (FD) in clinical trials, particularly in alleviating meal‐related symptoms. In the present study, we examined the gastrointestinal prokinetic effects of acotiamide administered orally or intraduodenally in conscious dogs and investigated in vivo and ex vivo anti‐AChE activity of acotiamide to clarify its mechanism of prokinetic action. Methods Gastrointestinal motility was measured in conscious dogs with chronically implanted force transducers. Key Results Oral administration of acotiamide stimulated postprandial gastroduodenal and colonic motor activities. Measurement of gastrointestinal motility showed that acotiamide, like itopride and mosapride, enhanced gastric antral motility. Further, acotiamide markedly improved clonidine (an α₂‐adrenoceptor agonist)‐induced hypomotility in a dog model of gastric motor dysfunction. The postprandial gastric antral motility enhanced by acotiamide was completely abolished on treatment with the muscarinic receptor antagonist atropine. Results of an in vivo experiment on anti‐AChE activity showed clearly increased acetylcholine‐induced gastric motility on intraduodenal administration of acotiamide, just as observed with the AChE inhibitor neostigmine. Further, in ex vivo experiment, intraduodenal administration of acotiamide significantly inhibited AChE activity in canine gastric antrum. Conclusions & Inferences Our findings revealed that acotiamide administered through the alimentary tract exerts gastroprokinetic action via cholinergic pathways by inhibiting AChE activity. These results may also confirm the mechanism of action in clinical efficacy of acotiamide on FD.     

Sympathetic response to stimulation of the pontine A5 region in conscious rabbits

Studies in anaesthetized animals have shown that the pontine A5 noradrenergic region plays an important role in the sympathetic control of arterial pressure (AP). The aim of this study was to develop, in conscious rabbits, a technique for microinjections into the A5 region and examine the effects of stimulation of this region on renal sympathetic nerve activity (RSNA). In preliminary mapping experiments on four anaesthetized rabbits, electrical stimulation of the A5 region induced a pressor response ranging between 25 and 75 mmHg while unilateral injection of glutamate (100 nmol) did not change AP. The mapping experiments were used to enable guide cannulae implantation for subsequent microinjections into the A5 region. In six conscious rabbits, unilateral injection of glutamate (100 nmol) caused a consistent increase in RSNA (+45%) but did not change AP. In another eight rabbits, bilateral injection of glutamate (0.3, 3, 30 nmol) into the A5 region dose-dependently increased RSNA by 13%, 30% and 40%, respectively. In four rabbits, angiotensin II (0.3, 3, 30 pmol) injected bilaterally into the A5 region increased RSNA by 5%, 22% and 28%, respectively. In all animals the increase in RSNA was mainly mediated by increasing amplitude of sympathetic synchronized bursts while their frequency remained unchanged. However, both glutamate and angiotensin II did not change AP indicating that the sympathoexcitatory response to the A5 stimulation might be relatively confined to the renal bed. Using a novel microinjection technique developed for conscious rabbits, we found that the A5 region may provide an important excitatory and possibly selective input to the renal sympathetic preganglionic neurons.     

Involvement of central dopamine and D1 receptors in stress-induced colonic motor alterations in rats.

The role of central versus peripheral influence of dopamine (DA) in the genesis of emotional stress (ES) induced by fear to receive electric footshocks on colonic motility was evaluated in rats equipped with implanted electrodes on the proximal colon. In control rats, the frequency of colonic spike bursts increased from 7.5 +/- 1.9 to 16.0 +/- 2.1 per 10 min when the rats were placed in a test box where they had previously received electric footshocks. This increase induced by ES was significantly p less than 0.05, reduced by previous ICV or IP administration of (+)SCH 23390 (a D1 receptor antagonist) at doses of 10 and 100 micrograms/Kg, respectively. Although sulpiride (a D2 antagonist) injected ICV or IP at similar doses had no effect on the ES-induced increase in the frequency of colonic spike bursts. DA (100 micrograms/kg), and the selective D1 (SKF 38383) or D2 (quinpirole) receptor agonist injected ICV at a dose of 5 micrograms/kg also increased significantly by 48.7, 54.8, and 68.7%, respectively, the colonic spike burst frequency whereas they are inactive when injected IP at similar and higher doses. These results suggest that, in rats, (a) emotional stress stimulates colonic motility through the stimulation of dopaminergic neurons involving D1 receptors and (b) exogenous activation of central D1 and D2 receptors similarly stimulate colonic motility by increasing the occurrence of colonic spike bursts.     

Antral motility measurements by magnetic resonance imaging

Magnetic resonance imaging has been recently proposed as a promising, noninvasive technique to assess the motility of the gastric antrum. However, so far the reproducibility and dependence on test meal composition has not been evaluated. In this study, snapshot echo-planar magnetic resonance imaging was used to measure the frequency, propagation speed and percentage occlusion of antral contractions in 28 healthy volunteers. They were fed either liquid (n=12), mixed liquid/solid (n=8) or mixed viscous/solid (n=8) nutrient (1350 kJ) test meals, and a total of 208 motility measurements were performed. No effect of meal type on antral motility parameters was observed. Antral contraction frequency was 3.0 +/- 0.2 min(-1) (mean +/- SD, n=164), propagation speed was 1.6 +/- 0.2 mm s(-1) (n=164) and the percentage occlusion was 58 +/- 14% (n=76). Overall, 21% of measurements did not provide useful antral motility data, because, in the supine position, the antrum was not filled by the test meal. Simple methods to overcome this and reduce scanning time to a minimum are proposed. The results show that the noninvasive magnetic resonance imaging evaluation of antral motility is accurate and reproducible and has potential to become a standard tool for such investigations.     

Involvement of NO in gastric emptying of semi-solid meal in conscious pigs

The influence of non-selective nitric oxide synthase (NOS) inhibition on gastric emptying of a semi-solid meal was studied in conscious pigs. Antroduodenal motility and fundic compliance were also assessed to evaluate the mechanisms at the origin of potential alteration in gastric emptying pattern. N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg kg(-1) i.v.) delayed gastric emptying (half-emptying time of 128.98 +/- 16.86 min vs 73.74 +/- 7.73 min after saline, P < 0.05, n = 6) as a result of decreased proximal gastric emptying. No changes were observed for distal gastric emptying as a result of unchanged antral motility. Similarly, no changes were noted on duodenal motor patterns either in the fasted or in the fed state. L-NAME decreased fundic compliance in fasted state (49 +/- 11 mL mmHg(-1) vs 118 +/- 15 mL mmHg(-1) after saline, P < 0.05, n = 6). As this phenomenon is expected to increase emptying rate, the gastroparesis induced by NOS inhibition is thus likely to originate from distal resistive forces. It is concluded that NO positively modulates gastric emptying.     

The transmission mechanism of the vagal control of the feline pylorus

Summary Gastric motility and pyloric contractility were studied in laparotomized cats under chloralose anaesthesia by recording the intragastric volume and changes in an applied constant transpyloric flow of body-warm saline. Unilateralefferent electrical stimulation of the cervical vagi resulted in a prompt gastric contraction and a delayed pyloric contraction. In one third of the animals abiphasic pyloric motor response, consisting of a short period of increased flow preceding the longlasting decrease or cessation of the flow was observed. Afteratropine (0.2 mg/kg b.w.) the vagal nerve stimulation resulted in agastric relaxation, while the biphasic pyloric motor response was even more pronounced, with a significantly longer latency of the contractile phase. Addition ofguanethidine (2 mg/kg b.w.) did not affect these motor responses. Afterhexamethonium (25 mg/kg i.v. and 50±10 mg per kg i.a. b.w.) the stimulation procedure still resulted in a slight gastric relaxation, while the pyloric contraction was effectively blocked. However, the relaxatory phase required theaddition of atropine to become antagonized indicating separate transmission mechanisms for the relaxatory and contractile components of the pyloric motor response at efferent vagal stimulation.When the pyloric motor response atafferent cervical vagal nerve stimulation was studied, using similar parameters, amonophasic pyloric contraction was obtained, which in all animals was antagonized by hexamethonium and infrequently by atropine. The results obtained indicate that not only classical cholinergic receptors, but also nonclassical (e.g. peptidergic receptors) are involved in the complex pyloric motor responses at efferent Stimulation. The pyloric contraction obtained at afferent stimulation was, however, possible to block with hexamethonium, indicating a transmission via ganglionic receptors.     

Vagal mechanisms controlling serotonin release from the gastrointestinal tract and pyloric motor function

This chapter focuses on investigations of two mechanisms controlled by the vagal nerve; serotonin (5-HT) release from the small intestine and pyloric motor function. Morphological, physiological, pharmacological and biochemical methods were combined in these studies. 5-HT is mainly stored in enterochromaffin cells (EC), but is present also in mast cells and nerve terminals of the gut, as observed by immunocytochemistry. Vagal nerve stimulation causes a release of 5-HT from EC to the portal circulation and to the gut lumen. Morphological evidence for the endoluminal release of 5-HT was obtained by autoradiography and immunofluorescence. The 5-HT release from EC is mediated by a beta-adrenoceptor mechanism via sympathetic adrenergic fibers in the vagal nerve, originating from sympathetic ganglia, e.g. the superior cervical ganglion. This vagal adrenergic pathway was studied by fluorescence microscopy and retrograde tracing of horseradish peroxidase. The vagal peptidergic (nonadrenergic, noncholinergic) control of pyloric motor function was studied in chloralosed cats by means of an in vivo model, where changes of an applied flow of body-warm saline through the pylorus were recorded. Also, gastric volume changes were monitored. By means of immunofluorescence the presence of VIP-, enkephalin (ENK)- and substance P (SP)-like immunoreactivity was demonstrated in pyloric neurons and in the vagal nerve. Physiological evidence for a vagal VIPergic relaxatory mechanism was obtained, while ENK-neurons seem to mediate the vagally induced pyloric contraction, prevented by naloxone pretreatment. SP may mediate part of the vagally induced pyloric and gastric contraction, the latter probably via axon collaterals on final cholinergic neurons. ENKergic and SPergic vagal contractile mechanisms seem to be additive for the pylorus.     

The effect of Taraxacum officinale on gastric emptying and smooth muscle motility in Rodents

Background Taraxacum officinale (TO) is a traditional herbal medicine that has been widely used for abdominal illnesses. However, the efficacy and the mechanism of TO on gastric emptying (GE) and smooth muscle motility are unknown. Methods Ethyl acetate fraction (EA), n‐butanol fraction (BF), and aqueous fraction (AF) were prepared in succession from 70% ethanol extract (EE) of TO using solvent polarity chromatography. Phenol red meal was adopted to estimate GE in mice. A polygraph was used to measure the smooth muscle motility in rats. Key Results The percentage of GE was 48.8 ± 6.1% (vehicle control), 75.3 ± 6.5% (cisapride positive control), 68.0 ± 6.7% (EE), 53.3 ± 6.0% (EA), 54.1 ± 6.3% (AF), and 86.0 ± 6.5% (BF). Thus, BF was determined to be most effective in accelerating GE. This stimulatory effect of BF on GE was also supported by the observation that BF increased spontaneous contraction of gastric fundus and antrum and decreased the spontaneous motility of pyloric sphincter in vitro. Atropine blocked the stimulatory effect of BF on GE, whereas phentolamine and propranolol had no effect. Conclusions & Inferences BF seems to be a promising prokinetic agent. BF‐induced increase in the contraction of fundus and antrum contributes to an increase in the intra‐gastric pressure. BF‐induced decrease in the motility of pyloric sphincter contributes to a decrease in the resistance of food from the stomach to the small intestine. The acceleration of GE by BF is likely to be exerted through cholinergic stimulation.     

Video-based spatio-temporal maps for analysis of gastric motility in vitro: effects of vagal stimulation in guinea-pigs

Our aim was to evaluate topographically specific gastric motility changes induced by graded vagal activation. A recently developed method of constructing spatio-temporal maps of motility from video movies was adapted to the in vitro perfused guinea-pig stomach with an intact vagal nerve supply. In the unstimulated preparation, spontaneous activity was low or absent. Bilateral vagal stimulation with frequencies as low as 0.2 Hz triggered weak anally, and in some cases orally, propagating antral contractions at rates of about 5-6 min-1. Upon stimulation with higher frequencies, antral contractions increased significantly in length (starting more proximally) and amplitude, and produced large pressure peaks of up to 25 hPa, with maximal effects at 2-4 Hz. In contrast, the speed of propagation and the interval between peristaltic waves did not change with vagal stimulation at any frequency. Vagal stimulation also produced a significant and frequency-dependent enlargement of the fundus with a maximal effect at 4 Hz. It is concluded that a very low tonic vagal activity is apparently necessary and sufficient to express basic antral motility, while more sustained vagal activity is necessary for high-amplitude gastric contractions and significant sustained fundic relaxation. The constant interval between propagating contractions supports the concept that vagal input impinges on intrinsic enteric neural circuits that have a modulatory role in the myogenic mechanism underlying slow-wave peristalsis, rather than directly on gastric musculature.