Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Bethanechol Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed1984

Evidence for a direct action of acetylcholine on the gastric oxyntic cell of the amphibian.

The possibility of a direct action of acetylcholine (ACh) on the oxyntic cell not mediated by histamine release was studied in resting isolated gastric mucosae. H+ secretion and histamine release, and their relationship, were studied under ACh stimulation and other conditions. ACh released histamine from mucosal stores and stimulated H+ secretion. H2-receptor blocker cimetidine largely inhibited ACh-induced stimulation of H+ transport but not histamine release. Atropine inhibited the cholinergic response in both histamine release and H+ secretion. The dose-response curves to ACh showed nonparallel increases in H+ secretion and histamine release. When dose-response curves to exogenous and endogenous histamine (released by ACh) were compared, it was found that ACh increased Vmax for endogenous histamine. Comparison of the effects of ACh with other experimental conditions such as tetragastrin treatment, K+ depolarization, or Na+-free nutrient solution showed that the amount of histamine released by ACh was insufficient to explain the observed rates of secretion. Stimulation by ACh was faster, greater, and more transitory compared with that by histamine. In mucosae maximally stimulated by histamine, ACh induced a further increase in H+ secretion. In the presence of cimetidine, potentiation between ACh and dibutyryl cAMP or isobutyl-methylxanthine was found. The results are consistent with ACh having a dual action on oxyntic and histamine-releasing cells. The action of ACh on the oxyntic cell would potentiate the effect of released histamine. It is suggested that ACh and released histamine act on the oxyntic cell through different second messengers, resulting in the potentiated response.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Interaction between stimulants of exocrine pancreatic secretion in dogs.

We measured bicarbonate and protein secretory responses to graded doses of intravenous caerulein and bethanechol and intraduodenal L-phenylalanine alone or with background secretin; graded doses of secretin alone or with background caerulein or L-phenylalanine; and background secretin plus graded doses of caerulein or L-phenylalanine plus background atropine sulfate. Potentiation (more-than-additive response) occurred for bicarbonate secretion between secretin and caerulein, between secretin and L-phenylalanine, but not between secretin and bethanechol. The only potentiating interaction for protein secretion was between secretin and low doses of caerulein. Atropine abolished the potentiated bicarbonate response to secretin plus L-phenylalanine but had no effect on the response to secretin plus caerulein. Potentiation between secretin and cholinergic mechanisms and cholecystokinin for pancreatic bicarbonate secretion may be an important regulatory mechanism, while potentiation of protein secretion with these stimulants does not appear to be important in dogs. A cholinergic mechanism mediates much of the bicarbonate potentiation between secretin and intestinal L-phenylalanine.

Animals↗
PubMed1984

Influence of enteric cholinergic neurons on mucosal transport in guinea pig ileum.

Electrical field stimulation was used to activate enteric neurons in the guinea pig ileum in order to determine the involvement of intramural cholinergic motor neurons in the control of mucosal sodium and chloride transport. Rectangular, bipolar stimulus pulses evoked a tetrodotoxin-sensitive biphasic increase in short-circuit current (Isc) that was due to an increase in active chloride secretion without any effect on active sodium absorption. During activation of enteric neurons, atropine, in concentrations of 5 X 10(-8) M or higher, reversibly abolished the rapid phase of the Isc and reduced the maximum sustained response to 40-50% of control values. Atropine reduced chloride secretion evoked by electrical stimulation and had no effect on sodium fluxes. Basal rates of sodium and chloride transport and tissue conductances were not altered by atropine. When muscarinic receptors were maximally stimulated with 10(-5) M carbachol, activation of enteric nerves increased Isc to 46% of control values. Bethanechol and eserine increased base-line Isc, and this effect was blocked by atropine but not by tetrodotoxin. The increase in Isc evoked by bethanechol was due to an increase in active chloride secretion. These results show that acetylcholine released by activation of enteric cholinergic motor neurons acts as muscarinic receptors on enterocytes to stimulate chloride secretion.

Acetylcholine↗
PubMed1984

Pancreatic polypeptide inhibits exocrine pancreatic responses to six stimulants.

We determined the effects of three different doses of pancreatic polypeptide (50, 200, and 800 pmol X kg-1 X h-1) on pancreatic responses to graded doses of intravenous secretin, caerulein, and bethanechol and intraduodenal HCl, L-phenylalanine, and sodium oleate in dogs. The two lowest doses of pancreatic polypeptide (PP), which produced blood levels lower than measured after a meal, significantly inhibited the pancreatic responses to secretin, caerulein, HCl, and L-phenylalanine; the highest dose of PP inhibited the responses to bethanechol and sodium oleate. There was no difference in the degree of inhibition of bicarbonate or protein secretion caused by pancreatic polypeptide. With secretin, caerulein, bethanechol, and sodium oleate, inhibition was most pronounced against lower doses and was surmountable with higher doses of these stimulants. Inhibition of responses to HCl and L-phenylalanine was observed at all doses of these stimulants. Inhibition of the exocrine pancreatic secretory responses to six different stimulants by PP suggests that this hormone may play an important role in regulation of postprandial pancreatic secretion.

Animals↗
PubMed1984

Bethanechol prevents inhibition of gastric acid secretion by gastric inhibitory polypeptide.

Earlier studies of gastric inhibitory polypeptide (GIP) have shown that it is a powerful inhibitor of acid secretion in denervated gastric pouches. Other studies, however, have shown that it is a weak inhibitor in innervated stomach preparations. In this study we evaluated the inhibitory action of GIP in four dogs, each provided with both a vagally denervated (Heidenhain) pouch and a gastric fistula of the innervated stomach. The effect of intravenous infusion of pure porcine GIP (1 microgram X kg-1 X h-1) on pentagastrin dose response was studied with and without background infusion of bethanechol (25 micrograms X kg-1 X h-1). GIP powerfully inhibited pentagastrin-stimulated acid secretion from the Heidenhain pouch but not from the gastric fistula. The maximal inhibition was 76% for the Heidenhain pouch and 29% for the gastric fistula. Despite the attainment of high levels of circulating immunoreactive GIP (greater than 3,000 pg/ml) early after the onset of infusion of the peptide, inhibition occurred relatively late, suggesting that this action of GIP might be mediated by the release of some other substance(s). Background infusion of bethanechol totally abolished the inhibitory action of GIP in both the Heidenhain pouch and gastric fistula.

Animals↗
PubMed1984

Age-related changes in colonic function in rats.

Aging in humans is associated with changes in gastrointestinal function. We wanted to determine whether a similar phenomenon occurs in rats and whether rats would be a suitable model to study changes in the gastrointestinal tract with age. Intestinal transit, response in vitro of circular colon strips to bethanechol and electrical stimulation, and colonic smooth muscle histology were compared for post-pubertal (5-12 mo) and senescent (25-28 mo) male Fischer 344 rats. Colonic transit of 51Cr was decreased 45% in senescent rats in comparison with younger rats. The maximum response of circularly oriented muscle strips from senescent rats to electrical stimulation of nerves was 32% less than the maximum response of strips from postpubertal rats. Likewise, the maximum response of the muscle strips to bethanechol was 16% less in the senescent group compared with the postpubertal group. There was no difference between the two groups in the EC50 of bethanechol. The thickness of the muscle layers and the percent circular muscle of strips fixed at optimum length were the same in both age groups. The senescent rat appears to be a useful model for the study of gastrointestinal changes with aging.

Aging↗
PubMed1985

Effects of sham feeding, bethanechol, and bombesin on somatostatin release in dogs.

In seven conscious dogs with esophagostomies and gastric cannulas, the acid, gastrin, and somatostatinlike immunoreactivity (SLI) responses to 5-min sham feeding with or without pretreatment with atropine sulfate (20 and 100 micrograms/kg) were measured. The responses to bethanechol (100 micrograms X kg-1 X h-1), to bombesin (0.5 micrograms X kg-1 X h-1) with or without pretreatment with atropine sulfate, and to a combined stimulation with bethanechol and bombesin were also measured. Sham feeding resulted in an increase in plasma SLI concentration (basal level, 20.4 +/- 4.2 pg/ml; maximally stimulated level, 46.8 +/- 5.6 pg/ml; P less than 0.01). After the injection of atropine the integrated SLI response to sham feeding was significantly decreased but not suppressed. Infusion of bethanechol did not alter SLI plasma levels. Bombesin infused alone increased the plasma SLI concentration (basal level, 15.6 +/- 2.3 pg/ml; maximally stimulated level, 55.6 +/- 10.3 pg/ml; P less than 0.01). The integrated SLI response to bombesin was significantly decreased by atropine but not significantly changed by bethanechol. These studies show that sham feeding and bombesin release somatostatin. They suggest that somatostatin release is largely under vagal-cholinergic control.

Animals↗
PubMed1985

Mediation of muscarinic stimulation of pepsinogen secretion in the frog.

The in vitro release of pepsinogen secretion by the isolated esophagus of the American bullfrog was studied with an improved model system. The tissue was mounted in a double chamber that preserves mucosal polarity and provides both control and test segments, each 1 cm2 from the same tissue. Pepsinogen secretion was severalfold higher than previously found with mucosal strips and could be sustained for several hours. Bethanechol (BCh) caused concentration-dependent (0.1-50 microM) pepsinogen secretion with a Vmax of 74 +/- 12 micrograms X mg prot-1 X h-1 or 50-60% of total pepsinogen; Km was 3 microM and 500 microM BCh stimulated at less than the Vmax value. Atropine specifically blocked BCh and pA2 = 9.3. In the presence of 100 microM isobutylmethyxanthine, BCh produced a dose-dependent increase in tissue cAMP but not cGMP. BCh remained effective in Ca2+-free medium. In calcium-free medium EGTA concentration dependently (0.2-5 mM) suppressed the pepsinogen response to BCh. The evidence thus far suggests that cholinergic stimulation of pepsinogen secretion in the tissue acts via both cAMP and Ca2+. More specific studies would be required for absolute confirmation of either or both apparent mechanisms and to resolve how they interact.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Role of cholecystokinin in pancreatic exocrine response to intraluminal amino acids and fat.

Controversy continues over the relative contributions made by hormonal and neural mechanisms in the exocrine pancreatic response to ingested food. The recent description of the drug proglumide as a specific, competitive cholecystokinin (CCK)/gastrin receptor antagonist has permitted reevaluation of the role of CCK in this process. In chronic pancreatic fistula dogs, dose-response studies were performed to determine the effect of proglumide on the pancreatic responses to octapeptide of CCK (CCK-OP), intravenous bethanechol, intraduodenal amino acids, and intraduodenal fat. Pancreatic volume, protein, and bicarbonate outputs to all doses of CCK-OP were inhibited significantly (P less than 0.05) in a competitive manner, consistent with the proposed mode of action of proglumide. In contrast, proglumide caused only minor and insignificant inhibition of the output responses to intravenous bethanechol. Virtually complete inhibition to all doses of intraduodenal amino acids and fat was observed with proglumide administration. If indeed proglumide is a specific CCK receptor antagonist, these results support the hypothesis that CCK is the major mediator of the intestinal phase of exocrine pancreatic secretion.

Amino Acids↗
PubMed1985

Interaction between stimuli and their antagonists on frog esophageal peptic glands.

The peptic glands, which are located in the mucosa of the distal esophagus in the frog, respond to multiple stimuli. In vitro studies were performed, using mucosal sheets of the esophagus of Rana catesbeiana, during the summer months when the glands are fully responsive to determine whether the receptors for the stimuli [cholinergic, beta-adrenergic, and peptidergic (bombesin but not cholecystokinin)] are specific to the stimuli. Through the use of three classes of antagonist, we found that 1) atropine defined the muscarinic nature of the bethanechol stimulation, 2) propranolol defined the beta-adrenergic nature of stimulation by isoproterenol, and 3) the substance P analogue [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P was specific for the peptide bombesin. No cross-inhibition was seen, and dibutyryl cGMP did not inhibit any of the three stimuli. Moreover, any two of the three stimuli in combination stimulated more pepsinogen than either alone but the same as the sum of the two individual responses. Both lines of evidence indicate that there are at least three independent receptor pathways for stimulation of pepsinogen secretion in these glands.

Animals↗
PubMed1986

Calcitonin gene-related peptide-induced selective inhibition of gastric acid secretion in dogs.

Calcitonin gene-related peptide (CGRP) is a 37-residue peptide recently characterized in the brain and found in high concentrations in the gut, particularly in the stomach and pancreas. The effects of intravenous infusion of human and rat CGRP (260 pmol . kg-1 . h-1) on gastric secretion and emptying and pancreatic exocrine secretion were studied in conscious dogs. CGRP inhibited by 60-75% gastric acid secretion stimulated by a meal, sham feeding, or step doses of bombesin but did not modify acid response to step doses of histamine or bethanechol. The inhibitory effect of CGRP is not due to blockage of postprandial or bombesin-stimulated gastrin release. CGRP did not influence basal or meal-stimulated pancreatic exocrine secretion or the rate of gastric emptying of a saline meal. These results indicate that CGRP is a potent and selective inhibitor of gastrin-mediated acid secretion in dogs and, under these conditions, did not alter other gastrointestinal functions such as gastric emptying or pancreatic exocrine secretion.

Animals↗
PubMed1986

Effect of selective muscarinic antagonists on peristaltic contractions in opossum smooth muscle.

In this study we examined the role of M1- and M2-muscarinic receptors in the mediation of circular smooth muscle esophageal contractions elicited by pharmacological cholinergic stimulation and during peristalsis in anesthetized opossums. Esophageal-body contractions were induced by bethanechol administration, whereas peristalsis was elicited by pharyngeal stroking or cervical vagal stimulation. Contractions were measured by a low-compliance manometric recording system. The incidence and amplitude of bethanechol-induced contractions were antagonized by 4-diphenylacetoxy-n-methylpiperidine (4-DAMP) and atropine but not pirenzepine. 4-DAMP and atropine caused an increased velocity, decreased amplitude, and preferential reduction of the incidence of primary peristaltic contractions in the proximal smooth muscle esophagus. During long-train vagal stimulation, intra-stimulus A-waves had a velocity similar to primary peristalsis, whereas poststimulus B-waves showed a velocity considerably faster than primary peristalsis. Short-train vagal stimulation produced a contraction sequence, termed an "S-wave," that had a velocity similar to that of the A-wave. At low doses 4-DAMP increased the velocity and decreased the amplitude of A-wave and S-wave contractions, and at high doses 4-DAMP abolished both the A-wave and S-wave contractions. B-wave contractions were minimally affected by 4-DAMP. Pirenzepine had no effect on contractions induced by swallows or vagal stimulation. We conclude that M2-muscarinic receptors mediate esophageal contractions in the circular smooth muscle during primary peristalsis and during A-waves and S-waves induced by vagal stimulation, and M1-receptors do not have any important role in the excitatory neural pathway to the esophagus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Salivary response to food in humans and its effect on gastric acid secretion.

The purpose of these studies was to determine the amount of saliva secreted in response to food in humans and to evaluate the effect of saliva on postprandial gastric acid secretion. Subjects chewed and spat out an appetizing steak and french-fried potato meal (modified sham feeding), with the increase in the weight of the meal during sham feeding taken to represent salivary secretion. Mean salivary flow rose from basal rates of 37.1 ml/h to 167.3 ml/h during modified sham feeding (P less than 0.001). Chewing gum increased salivary secretion to approximately the same extent as modified sham feeding, whereas chewing on plastic tubing caused a much smaller increase in salivary flow. Intravenous infusion of bethanechol (50 micrograms . kg-1 . h-1) was approximately half as potent as modified sham feeding or gum chewing in stimulating salivary flow. The salivary response to sham feeding was completely blocked by 15 micrograms/kg intravenous atropine. Salivary secretion increased approximately 20 ml/h when a 700-ml amino acid meal was infused directly into the stomach (P less than 0.01), whereas gastric distension with 700 ml saline had no effect. These findings suggested that food in the stomach or upper small intestine may activate a reflex or release a hormone into the circulation that augments salivary flow. Although intravenous gastrin-17 infusion had no effect on salivary flow, somatostatin-14 infusion increased salivary flow 15 ml/h (P less than 0.02). Saliva contained approximately 2,000 pg/ml immunoreactive urogastrone, an inhibitor of acid secretion when administered parenterally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Cellular messengers of stimulants of pepsinogen secretion from isolated frog esophageal mucosa.

The messenger roles of Ca2+ and cyclic nucleotides in the stimulation of pepsinogen secretion by three classes of stimuli [muscarinic (bethanechol), peptidergic (bombesin), and adrenergic (isoproterenol)] were studied in vitro using the peptic gland-bearing esophageal mucosa from the American bullfrog, Rana catesbeiana. Pepsinogen secretion was stimulated in a dose-dependent manner by the calcium ionophore A23187, by dibutyryl cAMP (DBcAMP), and by isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor. Isoproterenol and bethanechol increased the tissue cAMP content in the presence of IBMX. IBMX, which by itself stimulated secretion, was potentiating in combination with bombesin, additive with bethanechol, and less than additive with isoproterenol. Omission of Ca2+ from the bathing medium did not alter basal pepsinogen secretion nor the response to maximally effective doses of isoproterenol but partly inhibited the secretory responses to bethanechol and bombesin. Ca2+-free medium with 1 mM EGTA reduced pepsinogen secretion under all basal and stimulated (including A23187- but not DBcAMP-stimulated) conditions, indicating a critical role for Ca2+ in the secretion of pepsinogen secretion. A23187 by itself produced only an initial (15-20 min) release of pepsinogen, whereas IBMX and DBcAMP produced a delayed sustained secretion. The combination of A23187 with either IBMX or DBcAMP mimicked the responses to bethanechol or bombesin. These results indicate that both calcium and cAMP may be obligatory and interacting intermediates in the full stimulation of pepsinogen secretion by frog esophageal peptic glands with at least cholinergic and peptidergic stimuli.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Seasonal fluctuations in pepsinogen secretion from frog esophageal peptic glands.

The seasonal activity of pepsinogen secretion in the Rana catesbeiana was studied by use of peptic gland bearing esophageal mucosa mounted in a perfused double chamber. The amount of the basal pepsinogen secretion during hibernation (winter) and breeding (spring) periods was approximately 25 and 55% of basal secretion during the active (summer) period. The circumannual variation of basal secretion was highly correlated (r = 0.88, n = 37) with the pepsinogen content of the mucosa. The fractional rate of basal secretion (approximately 2% of content per hour) remained essentially constant, and pepsinogen as a fraction of total protein remained at between 20 and 25%. The results indicate that the decrease in absolute basal secretion from frog peptic glands during winter is a consequence of decreased content and hence synthesis of protein, including pepsinogen, by the mucosa. In addition, stimulated secretory responses to both bethanechol and bombesin, as a multiple of basal rate, were reduced during both hibernation and breeding periods, whereas the response to isoproterenol was entirely abolished during the hibernation period. By contrast, the secretory response to isobutylmethylxanthine remained constant (approximately 200% of basal) through all seasons, suggesting that mechanisms responsible for enzyme translocation and secretion remained intact. Reduced basal and secretagogue-stimulated secretion during hibernation and breeding seasons is thus likely due to a combination of reduced protein synthesis and decreased number or function of agonist receptors in peptic cells of the frog.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Regulation of muscarinic acetylcholine receptors in cultured guinea pig pancreatic acini.

Regulation of muscarinic receptors in cultured guinea pig pancreatic acini was investigated by assessing the effects of cholinergic agonists on binding of [N-methyl-3H]scopolamine [( 3H]NMS) and on amylase release. Freshly dispersed acini bound [3H]NMS with a Kd of 74 pM and a maximal binding level (Bmax) of 908 fmol/mg DNA. Carbachol (CCh) stimulated amylase secretion and inhibited [3H]NMS binding. Incubation of acini for 30 min with 0.1 mM CCh decreased the subsequent efficacy of CCh in stimulating amylase release by threefold but had no effect on its potency. In contrast, amylase release in response to cholecystokinin octapeptide (CCK-8) was not altered by CCh preincubation. [3H]NMS binding to acini was decreased only 15-20% after 30-min incubation with CCh. However, culture of acini with 0.1 mM CCh decreased [3H]NMS binding by 50% at 3-4 h and by 85-90% at 24 h. This decrease was attributable primarily to a reduction in Bmax. [3H]NMS binding also was decreased to a similar extent by the cholinergic agonists bethanechol and methacholine but not by other secretagogues. The decrease in antagonist binding induced by CCh was dose dependent, with the IC50, 5.8 microM, approximating the EC50 for amylase release, 4.3 microM. Culture of acini for 24 h with CCh abolished subsequent amylase release in response to CCh but not to CCK-8. When CCh was removed from the culture medium after 24 h and acini recultured in its absence, [3H]NMS binding increased with a half-time for recovery of 20-24 h; this recovery was blocked by cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1986

Inhibitory effects of beta-adrenergic agonists on gastric acid secretion in dogs.

We evaluated the effect of two beta-adrenergic agonists, isoproterenol (nonselective agonist) and terbutaline (selective beta 2-agonist), on gastric acid secretion stimulated by intravenous pentagastrin, bethanechol, or histamine in dogs with gastric fistulas. Intravenous infusion of isoproterenol or terbutaline inhibited pentagastrin-stimulated acid secretion to a significantly greater extent than they inhibited bethanechol- or histamine-stimulated acid secretion. For example, isoproterenol (12 micrograms X kg-1 X h-1) reduced mean pentagastrin-, bethanechol-, and histamine-stimulated acid output by 86, 63, and 14%, respectively. Percent inhibition of acid secretion with terbutaline (30 micrograms X kg-1 X h-1) averaged 60, 17, and 24% for pentagastrin, bethanechol, and histamine, respectively. Terbutaline also inhibited pentagastrin-stimulated acid secretion from vagally denervated fundic pouches in a dose-related manner. Plasma somatostatin-like immunoreactivity was significantly higher during infusion of terbutaline plus pentagastrin than during infusion of pentagastrin alone. However, an intravenous infusion of 0.3 microgram X kg-1 X h-1 somatostatin-14 had no effect on pentagastrin-stimulated acid secretion from the gastric fistula, even though this infusion increased plasma somatostatin-like immunoreactivity to the same extent as terbutaline plus pentagastrin infusion. Thus the amount of somatostatin released during terbutaline infusion was not sufficient to explain the inhibition of pentagastrin-stimulated acid secretion observed.

Adrenergic beta-Agonists↗
PubMed1986

Stimulation of oxyntic and histaminergic cells in gastric mucosa by gastrin C-terminal tetrapeptide.

Gastrin tetrapeptide (TG) stimulation of H+ secretion and histamine release and their relationship were characterized in isolated amphibian gastric mucosa. TG released histamine and stimulated H+ secretion. Dose-response curves to TG showed nonparallel increases in both parameters. In tachyphylaxis experiments, there was no correlation between histamine release and H+ secretion. Comparison of cimetidine inhibitory dose-response curves of maximal TG or histamine stimulation showed a much higher sensitivity for TG-stimulated H+ secretion. This suggests that the pericellular histamine concentration released by TG was lower than that needed for maximal response. In mucosae maximally stimulated by histamine, TG induced a further increase in H+ secretion. In the presence of cimetidine, there was potentiation between TG and dibutyryl cAMP that was dependent on the presence of extracellular calcium. The results are interpreted to indicate that TG (or gastrin) stimulates H+ secretion through different mechanisms: 1) direct stimulation of the oxyntic cell dependent on extracellular calcium, 2) potentiation between gastrin and histamine, and 3) release of histamine from paracrine cells. Direct stimulation of the oxyntic cell by TG is not sufficient to trigger H+ secretion. Potentiation between TG and histamine at the oxyntic cell may result from interaction between TG-induced increases in intracellular Ca2+ and histamine-induced increases in intracellular cAMP.

Animals↗