Effect of serotonin on bethanechol-stimulated gastric acid secretion and gastric antral motility in dogs

The purpose of the present study was to evaluate the effect of serotonin on bethanechol-stimulated gastric acid secretion and antral motility in conscious dogs with gastric fistula. Bethanechol stimulated the acid secretion dose-dependently and maintained the frequency and strength of the antral contractions at a high level. Serotonin inhibited the acid secretion dose-dependently, whereas the antral motility was stimulated. The acid inhibition was blocked by propranolol, and dose-response analysis showed inhibition of a non-competitive type. This study thereby shows that serotonin inhibits bethanechol-stimulated gastric acid secretion similarly to salmefamol (beta 2-adrenergic agonist)--that is, dose-dependently and non-competitively. Serotonin has been proposed to be a mediator of the beta-adrenergic influence on gastric function in vivo, but the counteracting effect of propranolol and the stimulatory effect of serotonin on motility contradict this hypothesis.     

Effect of Somatostatin on Pentagastrin-Stimulated Gastric Acid Secretion and Gastric Antral Motility in Dogs with Gastric Fistula

The purpose of the present study was to evaluate the effect of somatostatin on gastric acid secretion and gastric antral motility in conscious dogs with gastric fistula. Infusion of pentagastrin induced motility with a digestive pattern. Somatostatin inhibited dose-dependently the stimulated acid secretion, whereas the effect on antral motility was more complex, acting especially on the amplitude of the contractions. The effects of somatostatin were not altered by using α-and β-adrenergic, dopaminergic, and serotonergic blocking drugs. The dose-response kinetics with seven doses of pentagastrin with and without somatostatin showed inhibition of a competitive type for gastric acid secretion and of a non-competitive type for antral motility with regard to amplitude.     

Effect of serotonin on pentagastrin-stimulated gastric acid secretion and gastric antral motility in dogs with gastric fistula

The effects of exogenous serotonin on pentagastrin-stimulated gastric acid secretion and antral motility were evaluated with regard to inhibition kinetics and receptor mediation. Conscious gastric fistula dogs were used. Serotonin inhibited the acid secretion dose-dependently, whereas the antral motility was initially stimulated and thereafter inhibited. The inhibition of secretion was counteracted by different beta-adrenergic blocking drugs and methysergide, whereas the inhibition of antral motility was blocked by methysergide and indomethacin. Dose-response analysis showed inhibition of non-competitive types. This study supports the concept of differences in the regulation of gastric acid secretion and motility, but further experiments with simultaneous registration are required.     

Effect of Isoprenaline on Bethanechol-Stimulated Gastric Antral Motility in Dogs with Gastric Fistula

The purpose of the present study was to evaluate the effect of isoprenaline on gastric antral motility in conscious dogs with gastric fistula, using intraluminal strain-gauge transducers. Infusion of bethanechol increased the motility for both frequency and strength. Isoprenaline, a β₁- and β₂-agonist, was used alone and in conjuction with selective blockade of β₁ and β₂ receptors. The stimulated antral motility was dose-dependently inhibited by isoprenaline. The effect was significantly blocked by the β₁ + β₂-adrenoceptor blocker propranolol and by using in conjunction the β₁-adrenoceptor blocker practolol and the β₂-adrenoceptor blocker H 35/25. H 35/25 and particularly practolol reduced the effect of isoprenaline to some extent, but the reduction was not of statistical significance. This indicates that isoprenaline acts on antral motility through both β₂ and β₁ receptors. Dose-response experiments with five logarithmically increasing doses of bethanechol and one dose of isoprenaline showed inhibition of a non-competitive type.     

Exogenous serotonin and gastric mucosal blood flow in conscious dogs

The effects of serotonin on pentagastrin- and bethanechol-stimulated gastric mucosal blood flow (GMBF) and acid secretion were evaluated. Conscious gastric fistula dogs were used, with neutral red clearance as the method to estimate the mucosal blood flow. Serotonin inhibited the acid secretion, with a counteracting effect of propranolol and methysergide. Serotonin inhibited the pentagastrin- and bethanechol-stimulated GMBF after 15 min of infusion. The ratio between GMBF and acid secretion was increased during serotonin infusion, which suggests primary and independent changes in both variables. Propranolol and methysergide counteracted the serotonin inhibition of the GMBF. It may be concluded from this study that the acid-inhibitory effect of serotonin is not mediated by changes in the GMBF. The actions of serotonin on acid secretion and GMBF are mediated by specific receptors.     

Effect of somatostatin on bethanechol-stimulated gastric acid secretion and gastric antral motility in dogs with gastric fistula

The purpose of the present study was to evaluate the effect of somatostatin on gastric acid secretion and gastric antral motility in conscious dogs with gastric fistula. Infusion of bethanechol stimulated dose-dependently acid secretion, whereas the frequency and strength of antral motility was maintained at a high level. Somatostatin inhibited dose-dependently the stimulated acid secretion, whereas the effect on antral motility was more complex, acting especially on the amplitude of the contractions. The effects of somatostatin were not altered by using alpha-adrenergic, beta-adrenergic, dopaminergic, and serotonergic blocking drugs. The dose-response kinetics with four doses of bethanechol with and without somatostatin showed inhibition of a non-competitive type for gastric acid secretion and of a competitive type for antral motility with regard to amplitude.     

Effect of somatostatin on pentagastrin-stimulated gastric acid secretion and gastric antral motility in dogs with gastric fistula

The purpose of the present study was to evaluate the effect of somatostatin on gastric acid secretion and gastric antral motility in conscious dogs with gastric fistula. Infusion of pentagastrin induced motility with a digestive pattern. Somatostatin inhibited dose-dependently the stimulated acid secretion, whereas the effect on antral motility was more complex, acting especially on the amplitude of the contractions. The effects of somatostatin were not altered by using alpha- and beta-adrenergic, dopaminergic, and serotonergic blocking drugs. The dose-response kinetics with seven doses of pentagastrin with and without somatostatin showed inhibition of a competitive type for gastric acid secretion and of a non-competitive type for antral motility with regard to amplitude.     

Effect of dopamine on bethanechol-stimulated gastric antral motility in dogs with gastric fistula

The purpose of the present study was to evaluate the effect of dopamine on gastric antral motility in conscious dogs with gastric fistula, using intraluminal strain-gauge transducers. Infusion of bethanechol increased the motility with regard to both frequency and strength. Dopamine, an endogenous catecholamine, was used alone and in conjunction with selective blockade of adrenergic and dopaminergic receptors. The stimulated antral motility was dose-dependently inhibited by dopamine. The effect was significantly blocked by the peripherally acting dopaminergic blocker domperidone. The alpha-adrenoceptor blocker phentolamine reduced the effect of dopamine to some extent, but the reduction was not of statistical significance. The dopamine-inhibited motility was not altered by the beta 1-adrenoceptor blocker practolol or the beta 1 + beta 2-adrenoceptor blocker propranolol. This indicates that dopamine acts on gastric antral motility predominantly through dopaminergic receptors. beta-Adrenergic receptors, which are active in the impairment of gastric acid secretion, do not seem to be involved in the motility response. Dose-response investigations with five increasing doses of bethanechol and one dose of dopamine showed inhibition of a non-competitive type.     

Gastric motility is an important factor in the pathogenesis of indomethacin-induced gastric mucosal lesions in rats

Effects of atropine, cimetidine, and 16,16-dimethyl prostaglandin E₂ (16,16-dmPGE₂) on indomethacin-induced gastric lesions were investigated in rats by correlating their effects on gastric acid and HCO^}-₃ secretion and motility. Subcutaneously administered indomethacin (25 mg/kg) produced gastric mucosal lesions within 4 hr. In parallel studies, an equivalent dose of indomethacin inhibited gastric HCO^}-₃ secretion, and stimulated gastric motor activity measured as intraluminal pressure recordings, whereas acid secretion was unaffected. The lesions induced by indomethacin were significantly prevented by three agents: cimetidine (100 mg/kg), which reduced acid secretion; atropine (1 mg/kg), which reduced acid secretion and gastric motility; and 16,16-dmPGE₂ (10 g/kg), which reduced acid secretion and motility and increased gastric HCO^– ₃ secretion. If acid (150 mM HCl) was infused into the stomach (1.2 ml/hr) during indomethacin treatment, only the latter two agents significantly prevented the formation of gastric lesions in response to indomethacin. Since only the effect on gastric motility was common to these two agents (atropine and 16,16-dmPGE₂), the increased gastric motility may be an important pathogenetic factor in indomethacin-induced gastric lesions. The presence of acid as well as a deficiency of endogenous PGs may be prerequisite for later extension of the lesions but cannot account for the induction of mucosal lesions in rats following administration of indomethacin.     

Inhibitory Effect of Dopamine on Gastric Motility in Rats

Background: There is disagreement with regard to the involvement of dopamine (DA) receptors in gastric motility. The mechanism of the inhibitory effect of DA on rat gastric motility was investigated in association with acetylcholine (Ach) release in the present study.

Methods: In vivo vagotomized, splanchnicectomized rats and control rats were used, and gastric movement was determined as the gastric motility index after DA administration. In vitro study of Ach release from the circular muscle strips of the gastric corpus was investigated after administration of domperidone, SCH23390, phentolamine, or propranolol.

Results: In the in vivo study DA inhibited gastric motility in a dose-dependent manner. Vagotomy and splanchnicectomy had no effect on the inhibitory effect of DA. In the in vitro study DA inhibited [³H]-Ach release in a dose-dependent manner. The inhibitory effect of DA was antagonized by domperidone but not by phentolamine, propranolol, or SCH23390.

Conclusions: Inhibition of gastric motility by dopamine is independent of extrinsic innervation and seems to be mediated by DA₂ receptors in the gastric wall.     

Exogenous serotonin and histamine-stimulated gastric acid and pepsin secretion in dogs

The effects of serotonin on histamine-stimulated gastric acid and pepsin secretion were evaluated in conscious dogs with a gastric fistula. Histamine stimulated the acid secretion dose-dependently, whereas pepsin secretion was decreased by the high doses of histamine. The acid secretion was inhibited slightly by serotonin, with a maximum of 42% with a dose of 10 micrograms/kg/min. The pepsin secretion was only decreased non-significantly by serotonin, 10-15 micrograms/kg/min. The acid inhibition was counteracted by beta-adrenergic antagonists (propranolol, atenolol) and methysergide (serotonergic antagonist). The dose-response analysis showed inhibition of a competitive type. In conclusion, serotonin inhibits histamine-stimulated gastric acid secretion via serotonergic receptors and beta-adrenoceptors, whereas pepsin secretion is unaffected.     

Gastric Acid Inhibition by Antral Acidification Mediated by Endogenous Prostaglandins

The effects of indomethacin on the basal and stimulated gastric acid secretion at controlled intragastric pH were examined. Four tests with modified sham feeding were made in nine healthy volunteers on different occasions, twice with acid and twice with alkaline perfusion of the stomach. Blocking of the prostaglandin biosynthesis with indomethacin preceded one of the tests at each pH. Plasma levels of gastrin were measured. Antral acidification suppressed the basal and vagally stimulated gastric secretion rate of H⁺ and Cl^-. The inhibition was associated with a decreased plasma gastrin response. Indomethacin reduced the inhibition of the peak acid output and plasma gastrin levels induced by antral acidification. During alkalinization of the stomach indomethacin had no effect on the acid secretion rate or plasma gastrin levels. The results suggest that the pH-dependent inhibitory regulation of the gastric acid secretion is mediated by locally produced prostaglandins. The mechanism functions at least partially through modifying the release of gastrin.     

Effect of isoprenaline on bethanechol-stimulated gastric antral motility in dogs with gastric fistula

The purpose of the present study was to evaluate the effect of isoprenaline on gastric antral motility in conscious dogs with gastric fistula, using intraluminal strain-gauge transducers. Infusion of bethanechol increased the motility for both frequency and strength. Isoprenaline, a beta 1- and beta 2-agonist, was used alone and in conjunction with selective blockade of beta 1 and beta 2 receptors. The stimulated antral motility was dose-dependently inhibited by isoprenaline. The effect was significantly blocked by the beta 1 + beta 2-adrenoceptor blocker propranolol and by using in conjunction the beta 1-adrenoceptor blocker practolol and the beta 2-adrenoceptor blocker H 35/25. H 35/25 and particularly practolol reduced the effect of isoprenaline to some extent, but the reduction was not of statistical significance. This indicates that isoprenaline acts on antral motility through both beta 2 and beta 1 receptors. Dose-response experiments with five logarithmically increasing doses of bethanechol and one dose of isoprenaline showed inhibition of a non-competitive type.     

Gastric secretions affected by esophageal distention in the rat

Background  The effect of esophageal distention (ED) on gastric motility has been well documented, but only a few investigations have been carried out about the effect of ED on gastric secretions. The aim of this study was to investigate the effect of ED on gastric acid and pepsin secretions and the mechanisms involved. Methods  Male adult Wistar rats (200–240 g) were anesthetized by urethane [1.2 g/kg, intraperitoneally (i.p.)] and underwent tracheostomy and laparotomy. A catheter was inserted in the stomach through the duodenum for gastric washout and distention followed by the esophageal distention by a balloon (0.3 ml, 10 min). Gastric acid secretion was stimulated by gastric distension (1.5 ml/100 g body weight), pentagastrin (20 μg/kg, i.p.), or insulin (0.6 IU/kg, i.p.). Pepsin secretion was stimulated by carbachol (20 μg/kg, i.p.). Effects of cervical vagotomy and reserpine (1 mg/kg, i.p.) were also investigated. Results  Gastric distention-, pentagastrin-, and insulin-stimulated gastric acid secretion was reduced by esophageal distention (P < 0.001, P < 0.05, and P < 0.05, respectively). Carbachol-induced pepsin secretion was also attenuated by esophageal distention (P < 0.05). Cervical vagotomy abolished the inhibitory effect of ED on pentagastrin-induced gastric acid secretion. In reserpinized rats, ED reduced the basal gastric acid secretion (P < 0.05). Conclusions  These results indicate that the vagus nerves are involved in the inhibitory effect of esophageal distension on gastric secretory function.     

Motility-Related Cyclic Fluctuations of Interdigestive Gastric Acid and Bicarbonate Secretion in Man: A Source of Substantial Variability in Gastric Secretion Studies

The relationship between interdigestive gastric motility and secretion was studied in eight healthy volunteers. Acid and bicarbonate output rates were measured with a high time resolution, using a perfusion system based on continuous registration of pH and Pco₂ of gastric effluent. Antral pressure was measured by manometry. The total duration of the interdigestive motility cycle (time between two phase-Ill complexes) was 96 ± 12min (mean ± SE). In late migrating motor complex phase II, acid output, bicarbonate output, and bile reflux increased significantly. Acid secretion reached a peak in association with motor phase III. The gastric lumen was then rapidly alkalinized; this phenomenon was due to a simultaneous decrease in acid secretion and a short-lasting (15 ± 2min, mean ± SE) phasic increase in bicarbonate output, which was not associated with bile reflux (bilirubin). After these phase-III-related events both acid and bicarbonate output rates reached a relatively stable level during phase I and early phase II. This period of stability constituted 47 ± 3% (acid) and 41 ± 6% (bicarbonate, means ± SE), respectively, of the cycle. The peak to base line output ratio was 6.6 ± 1.2 (p < 0.001) for acid and 2.8 ± 0.3 (p < 0.001) for bicarbonate (means ± SE). The results show a marked variability in acid and bicarbonate output rates during the interdigestive motility cycle. The magnitude of this variability has previously been underestimated owing to poor time resolution of the secretion measurements. If not taken into account, these ‘spontaneous’ secretory variations may constitute a considerable source of error in gastric secretion studies.     

十二指肠胃化生与幽门螺杆菌相关性慢性胃炎

为从组织形态学角度评价幽门螺杆菌(HP)对胃酸分泌的影响,以231例胃体、胃窦及十二指肠粘膜活检病例为研究对象,探讨十二指肠胃化生(GM)与HP相关性慢性胃炎的感染部位、炎症活动度及萎缩之间的关系.结果表明HP在胃窦感染为主时十二指肠GM的发生增加;在冒体感染为主时则相反.十二指肠GM的程度与胃窦炎的活动度成正相关,与胃体炎活动度成负相关;胃窦粘膜萎缩时HP感染可减少十二指肠GM的发生.本文结果提示:HP在胃窦感染时能促进胃酸的分泌,而在胃体感染或胃窦粘膜萎缩时则可抑制胃酸分泌.     

Quantitation of Duodenogastric Reflux and Antral Motility by Color Doppler Ultrasonography: Study in Healthy Volunteers and Patients with Gastric Ulcer

Fujimura J, Haruma K, Hata J, Yamanaka H, Sumii K, Kajiyama G. Quantitation of duodenogastric reflux and antral motility by color Doppler ultrasonography. Study in healthy volunteers and patients with gastric ulcer. Scand J Gastroenterol 1994;29:897-902.

Background: Our objective was to develop a simple, noninvasive method for evaluating duodenogastric reflux, along with antral motility and gastric emptying of a liquid meal. Methods: Antral motility and gastric emptying were measured by ordinary ultrasonography after a meal of 400 ml consommé. Duodenogastric reflux was evaluated by means of color Doppler. In a preliminary in vitro study we demonstrated that the test meal (consommé) contained oil particles suitable as a marker for color Doppler. We then investigated duodenogastric reflux, antral motility, and gastric emptying of a liquid meal in 43 asymptomatic healthy volunteers and in 24 patients with gastric ulcer. Results: This approach was feasible in 65 (97.0%) of the 67 subjects studied. Duodenogastric reflux was demonstrated in 26 (61.9%) of the 42 healthy volunteers and in 20 (87.0%) of the 23 patients with gastric ulcer. The frequency of the duodenogastric reflux and the reflux index were significantly increased in patients with gastric ulcer as compared with asymptomatic healthy volunteers. Gastric emptying and the motility index of antral contractions were significantly decreased in patients with gastric ulcer as compared with asymptomatic healthy volunteers. Conclusions: Ultrasonography with color Doppler is useful for evaluating abnormalities of gastroduodenal motility and can be used to understand the pathogenesis of such disorders.     

Inhibition of Pentagastrin-Stimulated Gastric Acid Secretion by Acid Perfusion of the Duodenum in Chronic Gastric Fistula Rats

The effect of duodenal acid perfusion on pentagastrin-stimulated gastric acid secretion was studied in Sprague-Dawley rats provided with a chronic gastric fistula, gastroenterostomy, and a 4-cm blind duodenal loop anastomosed to the jejunum. During maximal acid stimulation with intravenous pentagastrin (16 μg·kg^?1 h^?1) the loop was perfused with 0.15 M NaCl or 0.05 M, 0.10 M, or 0.20 M HCl at a rate of 2 ml · h^?1. Perfusion with 0.05 M HCl did not significantly alter pentagastrin-stimulated secretion. 0.10 M and 0.20 M HCl reduced the 2-h acid response by 56% and 63%, respectively. Acid secretion returned to control level after cessation of acid perfusion. It is concluded that physiological amounts of HCl in the duodenum inhibits maximal acid secretion stimulated by pentagastrin in rats.     

Gastric acid inhibits antral phase III activity in duodenal ulcer patients

Fourteen patients with duodenal ulcers and eight healthy volunteers were examined to measure interdigestive gastroduodenal motility and plasma motilin. In order to study the effects of gastric acid on the gastroduodenal motility, 20 mg of famotidine was administered intravenously. The motility index of the gastric antrum and the duodenum, as well as the pH in the duodenal bulb were calculated. The duodenal pH was significantly lower and the gastric motility index was significantly weaker before the duodenal interdigestive migrating complex (IMC) in the ulcer patients than in the controls. Motilin levels increased before the duodenal IMC and decreased afterwards in both groups. Famotidine significantly increased the duodenal pH and the gastric motility index before the IMC, but no changes in the motilin level were noted. We conclude that duodenal ulcer patients have duodenal hyperacidity that results from increased inflow from the antrum and antral hypomotility during the gastric IMC and that these changes are normalized by the administration of famotidine. These results suggest that gastric acid inhibits antral contraction during the gastric IMC.     

Gastric Electrical Stimulation Does Not Significantly Affect Canine Gastric Acid Secretion and 24-Hour Gastric pH

Gastric electrical stimulation (GES) was shown to improve symptoms in patients with gastroparesis. However, the underlying mechanisms remain unclear. This study assessed the influence of various patterns of GES on fasting and postprandial gastric acid secretion and 24-hr gastric pH. Eight healthy dogs were studied and we found that in the fasting state, low-frequency, long-pulse (6/12-cpm, 375-msec, 4-mA) GES at the proximal stomach significantly inhibited the secretion of gastric juice (P < 0.05). No such effect was observed during GES (6/12 cpm) at the distal stomach. In the postprandial period, low-frequency, long-pulse GES at both proximal and distal sites and at both frequencies did not significantly affect gastric acid secretion. High-frequency, short-pulse GES, investigated for obesity (21 Hz, 8 mA, and 250 microsec, with 2 secs on, 3 sec off), at the proximal and distal stomach did not significantly affect the 24-hr gastric pH profile. In conclusion, GES with various stimulation parameters, and at various sites, has little effect on gastric acid secretion. The clinical effects induced by GES at these parameters may not be related to their effect on gastric acid homeostasis.