Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT02427 (Atropine)
 3,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the role of hormones in the control of pancreatic secretion, we developed, in seven dogs, a model of total extrinsic denervation of the jejunoileum by autotransplanting this segment of bowel. A Thomas-like cannula was placed into the stomach, the duodenum (to collect pure pancreatic juice), and the proximal part of the jejunum. Thus, intestinal stimulants could only stimulate the pancreas via release of humoral (= hormonal) mediators. Seven control dogs received only the three fistulas. After recovery, dose-response curves of pancreatic bicarbonate and protein response to perfusion of the extrinsically denervated or innervated jejunoileum with HCl (1.5 to 48 mmol h-1) were performed with and without atropine (14 nmol kg-1 h-1 i.v.). Plasma levels of secretin were determined by radioimmunoassay. The maximal bicarbonate output occurred in response to 24 mmol h-1 of HCl and was significantly (p less than 0.05) higher in intact as compared to denervated animals. Atropine only significantly depressed the bicarbonate response to HCl in dogs with a denervated jejunoileum. HCl caused a dose-dependent increase in plasma levels of secretin, which was not altered by denervation and/or atropine. Irrespective of the innervation of the small bowel, pancreatic protein output was only significantly stimulated above basal when high loads (12-48 mmol h-1) of HCl were given. Atropine significantly reduced these responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1991 May
PMID:Hormonal control of pancreatic secretion by intrajejunal HCl: studies in dogs with an autotransplanted entire jejunoileum. 186 69

We studied post-meal pancreatic secretion and gastrin release in conscious dogs with duodenal Thomas cannulas. Normal dogs were tested in physiological conditions and with an i.v. infusion of atropine 20 micrograms/kg/h or secretin 0.5 CU/kg/h. The responses were also studied after antral and truncal vagotomy. In the early phase (0-20 min) of the response, before gastric emptying started, antral vagotomy reduced fluid and protein outputs, and truncal vagotomy reduced them still more. Atropine reduced only the protein response. Gastrin release reached a peak after 20-25 min. After antral and truncal vagotomy, gastrin release was reduced within 10 min after the meal. Late-phase (greater than 20 min) pancreatic secretion depended on the presence of chyme in the duodenum. The effects of atropine and antral vagotomy in the cephalogastric phase could be explained by antropancreatic reflexes stimulating fluid secretion (atropine-resistant pathway) and protein output (atropine-sensitive pathway).
Pancreas 1991 Mar
PMID:The cephalogastric phase of the pancreatic response to food in the dog. 188 87

The effect of atropine on plasma cholecystokinin (CCK) and pancreatic secretion during intraintestinal infusion of a conventional defined formula liquid diet (Ensure HN, Ross Laboratories, 1.06 kcal/ml) was studied in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice, which were returned to the duodenum at all times. Pancreatic secretion was monitored during intraduodenal infusion of 0.15 M NaCl for 2 h followed by Ensure HN, both infused at 4.62 ml/h. Rats were infused i.p. with atropine (500 micrograms/kg/h) or vehicle throughout the experiment, beginning 1 h before monitoring of basal pancreatic secretion. Basal and 15 min postprandial plasma CCK concentrations were determined by bioassay. Atropine inhibited basal pancreatic protein secretion by approximately 60%. However, protein secretion during infusion of the diet was not decreased by atropine, due to a larger incremental pancreatic protein secretory response in atropine-treated rats. Plasma CCK 15 min after beginning the diet infusion was significantly increased by atropine (8.09 +/- 1.77 pM in atropine-treated rats versus 3.14 +/- 0.64 pM in controls). The results indicate that rats compensate for loss of cholinergic input to the pancreas by increasing CCK release in response to a meal. This is hypothesized to occur by virtue of reduced feedback inhibition of CCK release due to anticholinergic reduction of basal levels of intestinal protease activity.
Pancreas 1990 Sep
PMID:Atropine enhances food-stimulated CCK secretion in the rat. 223 72

To investigate the influence of the cholinergic nerves on the action of i.v. ethanol on interdigestive gastric acid, pancreatic enzyme, and bile acid output, seven healthy volunteers were studied. On each of 4 different days, they swallowed a multilumen intestinal tube system that allowed the measurement of intraluminal pressures and the collection of gastric and duodenal juice. The subjects received an i.v. infusion of either ethanol (600 mg/kg for 30 min followed by 3 mg/kg/min), atropine (5 mu/kg/h), a combination of both drugs, or NaCl. Whereas ethanol did not significantly influence motility, atropine induced motoric quiescence. Ethanol significantly (p less than 0.05) stimulated gastric acid output, by 55%, whereas atropine inhibited it by 91%. When ethanol and atropine were given together, gastric acid output was significantly higher than during atropine use alone. Both ethanol and atropine inhibited pancreatic amylase output--by 47% and by 82%, respectively. The degree of inhibition was 80% when ethanol and atropine were given simultaneously. Atropine but not ethanol significantly reduced bile acid output. The finding that atropine did not completely reverse the stimulating effect of i.v. ethanol on gastric acid secretion suggests that ethanol stimulates gastric acid secretion not only by a cholinergic but also by a noncholinergic mechanism. The observation that atropine did not reverse the inhibiting effect of ethanol suggests, but does not prove, that the effect of ethanol on the pancreas is predominantly mediated by cholinergic nerves.
Pancreas 1986
PMID:Action of intravenous ethanol and atropine on the secretion of gastric acid, pancreatic enzymes, and bile acids and the motility of the upper gastrointestinal tract in nonalcoholic humans. 243 66

Organophosphates (OPs) cause irreversible inhibition of cholinesterases (ChEs) and profound cholinergic stimulation. There are major differences in the response of the dog and cat pancreas to the in vivo administration of Diazinon (O,O-diethyl O-2-isopropyl-4-methyl-6-pyrimidyl phosphothioate), a butyrylcholinesterase (BuChE) inhibitor. Acute edematous pancreatitis is found in the dog but not in the cat. The present experiments were designed to see what effect OP had in vitro on pancreatic exocrine function of dog, cat, and guinea pig, and whether the effects were consistent with an anti-ChE activity. A water-soluble OP agent, tetraisopropyl pyrophosphoramide (iso-OMPA) at 10(-3) M, which like Diazinon inhibits BuChE, was used. Minced pieces of fresh whole pancreata 3 mm in size were taken from 3 dogs, 4 guinea pigs, and 2 cats. The tissues were placed in flasks containing Eagle's solution and gassed with 100% O2. Cumulative amylase release was measured by Phadebas method up to 3 h. At half-maximal acetylcholine (ACH) concentration (10(-5) M), the canine pancreas pretreated with iso-OMPA (10(-3) M) showed a 42-87% greater release of amylase than tissues receiving ACH alone (p less than 0.001). The same potentiated response to ACH was seen in guinea pig pancreas pretreated with iso-OMPA (p less than 0.001), but iso-OMPA pretreatment did not augment the ACH response in the cat. Atropine pretreatment effectively blocked all ACH responses, and there was no effect seen with iso-OMPA alone. In the dog, iso-OMPA in combination with half-maximal carbachol (10(-6) M), or in combination with half-maximal cholecystokinin (CCK-8) stimulation (10(-9) M), provided no potentiated amylase release.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancreas 1987
PMID:Effect of the organophosphate iso-OMPA on amylase release by pancreatic lobules of dog, guinea pig, and cat. 244 88

Five human pancreatic carcinoma cell lines were screened for the presence of muscarinic cholinergic receptors (mAChRs), using [3H]N-methylscopolamine ([3H]NMS). T3M4 and COLO-357 cells exhibited specific, high-affinity binding to mAChRs. A small amount of [3H]NMS also bound in PANCI and ASPC-I cells, but not in MIA PaCa-2 cells. Atropine, pirenzepine (PZ), and 11-[[2-[(diethylamino) methyly]-1-piperidinyl] acetyl]-5, 11-dihydro-6H-pyrido-[2, 3-b] [1, 4] benzodiazepine-6-one (AF-DX 116) inhibited [3H]NMS binding and carbachol-mediated [3H]inositol monophosphate formation in both T3M4 and COLO-357 cells. The order of inhibition was: atropine greater than PZ greater than AF-DX 116. Carbachol did not alter [3H]inositol monophosphate formation in the other cell lines. These findings suggest that the mAChRs expressed in some human pancreatic cancer cells exhibit the pharmacologic characteristics of a muscarinic receptor subtype with an intermediate affinity for PZ and a lower affinity for AF-DX 116 and are functionally coupled to activation of phospholipid hydrolysis.
Pancreas 1989
PMID:Identification and characterization of muscarinic receptors in cultured human pancreatic carcinoma cells. 273 80

We investigated the effects of oleic acid in the duodenum on pancreatic exocrine secretion and plasma secretin, and determined the role of cholinergic dependence on pancreatic secretion and secretin release in response to oleic acid in anesthetized rats. Oleic acid emulsion (pH 6.5) in three different doses of 0.06, 0.25, and 1 mmol/h was infused intraduodenally for 1 h with or without intravenous administration of atropine in a dose of 100 micrograms/kg/h. Intraduodenal administration of oleic acid resulted in significant increases in pancreatic juice volume and bicarbonate output, in a dose-related manner (p less than 0.001). Plasma secretin concentration caused dose-dependent elevation (p less than 0.001) by oleic acid, which correlated very well with bicarbonate output in response to oleic acid (p less than 0.001). Atropine inhibited pancreatic secretion including juice volume and bicarbonate output stimulated by oleic acid in each dose, statistically significantly (p less than 0.05-0.01), but did not affect plasma secretin concentration. Thus, we conclude that oleic acid in the duodenum stimulates pancreatic secretion and endogenous secretin release in rats, and that secretin release is not influenced by the cholinergic tone, although pancreatic secretory response is inhibited significantly.
Pancreas 1989
PMID:Effect of fatty acid on secretin release and cholinergic dependence of pancreatic secretion in rats. 276 74

Potentiating action between secretin and cholecystokinin on exocrine pancreatic secretion of bicarbonate has been well recognized. In the present study, we studied the effect of atropine on potentiating action on pancreatic exocrine secretion stimulated by exogenous secretin in physiologic dose and cholecystokinin-octapeptide in humans. Using a dye-dilution technique and a duodenal triple-lumen tube, pancreatic secretion of both bicarbonate and trypsin was determined while gastric juice was completely aspirated. Secretin given i.v. in a dose of 2.7 pmol/kg/h, which was known to achieve a similar plasma concentration of secretin after meal in humans, and cholecystokinin-octapeptide 26.2 pmol/kg/h potentiated pancreatic secretion of bicarbonate but not the pancreatic trypsin output. Atropine given i.v. in a dose of 1 mg/h abolished the potentiation effect of the two hormones on pancreatic bicarbonate output. Since the inhibitory effect of atropine on the secretin-stimulated bicarbonate output was statistically significant, the major inhibitory effect of atropine on the potentiation of pancreatic bicarbonate secretion appears to be its effect on the action of secretin.
Pancreas 1988
PMID:Atropine abolishes the potentiation effect of secretin and cholecystokinin-octapeptide on exocrine pancreatic secretion in humans. 336 47

We have investigated whether hormonally mediated negative feedback mechanisms regulate pancreatic exocrine secretion in guinea pigs. In anesthetized guinea pigs prepared with a tube in the proximal duodenum, pyloric ligation, and pancreatic duct cannulation with PE-10 tubing, diversion of pancreatic juice for as long as 4 h in fasting states failed to increase either pancreatic secretion or plasma levels of secretin or cholecystokinin (CCK). In the same animal preparation, intraduodenal (ID) infusion of sodium oleate (SO) resulted in significant increases in both pancreatic secretin and plasma levels of the two hormones that were significantly suppressed by ID infusion of pancreatic juice or a combination of trypsin and chymotrypsin. In another group of guinea pigs, this significant increase in pancreatic secretion was profoundly suppressed by a rabbit antisecretin serum (0.2 ml) or loxiglumide (10 mg.kg-1.h-1). Moreover, a combination of the antiserum and loxiglumide completely abolished the pancreatic secretion. The effect of atropine, 20 micrograms.kg-1.h-1 i.v., on SO-stimulated pancreatic secretion and hormone release was also studied. Atropine completely suppressed the pancreatic secretion of volume flow, bicarbonate, and protein stimulated by SO, whereas neither one of the two hormone levels was affected by intravenous atropine, indicating that atropine blocks the actions of both secretin and CCK on the pancreatic exocrine secretion. It is concluded that a negative feedback regulation of exocrine pancreatic secretion is operative in the intestinal phase of pancreatic secretion in guinea pigs and that this feedback mechanism is mediated by both secretin and CCK. Furthermore, in guinea pigs, cholinergic tone plays an important modulating role in the mechanism.
Pancreas 1995 Mar
PMID:Negative feedback regulation of pancreatic exocrine secretion in guinea pigs. 771 42

The response of the exocrine pancreas to intraduodenal perfusion of acetic and lactic acids in normal and previously atropinized rats was studied. Secretin and vasoactive intestinal peptide (VIP) plasma levels in portal plasma were also measured. Intraduodenal perfusion of both acetic and lactic acids significantly stimulated flow rate (from 0.29 +/- 0.03 microliters/min to a maximum of 1.06 +/- 0.08 microliters/min after acetic and from 0.35 +/- 0.05 microliters/min to a maximum of 1.13 +/- 0.12 microliters/min after lactic acid perfusion) and protein output (from 11.16 +/- 2.33 micrograms/min to a maximum of 35.1 +/- 7.4 micrograms/min after acetic and from 8.98 +/- 0.95 micrograms/min to a maximum of 22.5 +/- 1.3 micrograms/min after lactic acid perfusion). Atropine treatment significantly inhibited pancreatic flow rate and protein output after acetic acid perfusion, but no inhibition of flow rate and a slight decrease in the protein output after lactic acid perfusion were seen. With respect to plasma peptide concentrations, significant increases in secretin and VIP levels were found after perfusion of both organic acids; atropine administration significantly decreased plasma secretin levels after acetic acid administration although it did not affect plasma VIP concentrations. By contrast, atropine significantly increased plasma secretin levels, but significantly lower values of plasma VIP concentrations were observed after lactic acid perfusion. Therefore, cholinergic mechanisms are involved in the release of secretin and VIP and different types of control of exocrine pancreatic secretion occur, depending on the features of the intraduodenal stimulant.
Pancreas 1995 Jan
PMID:Cholinergic pathways are involved in secretin and VIP release and the exocrine pancreatic response after intraduodenally perfused acetic and lactic acids in the rat. 789 66


1 2 Next >>