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C Rozé

Publications and source records attributed to C Rozé.

At least 73 records · Page 4Linked to original sources
PubMed1990

Control of interdigestive and intraduodenal meal-stimulated pancreatic secretion in rats.

Mechanisms of neural (vagal and cholinergic) and hormonal [cholecystokinin (CCK)] control of pancreatic exocrine secretion were studied in basal interdigestive conditions and after stimulation by an intraduodenal meal in rats equipped with a semichronic pancreatic fistula. Bile was recirculated into the duodenum, and a solution of trypsin and electrolytes was continuously infused. Pancreatic secretion was compared in control experiments, after vagotomy, and after venous infusion of cholinergic and CCK antagonists. Basal pancreatic secretion was decreased by atropine, pirenzepine, and hexamethonium and to a lesser extent by vagotomy (protein output decreased more than fluid and HCO3- outputs). The CCK antagonists L364,718 and lorglumide had no effect on basal interdigestive pancreatic secretion. Small doses of atropine (8 and 25 micrograms.kg-1.h-1) did not modify the cumulated pancreatic response to the meal, whereas larger doses (75 and 225 micrograms.kg-1.h-1) increased it by 40-85%, according to the variables. Pirenzepine and hexamethonium did not modify the pancreatic response. Vagotomy had no effect on fluid and HCO3- responses and tended to increase protein response. L364,718 and lorglumide completely inhibited the protein response and decreased the fluid and HCO3- responses by 75 and 40%, respectively. L364,718 also suppressed the increased pancreatic response induced by atropine. This work confirms the prominent role of neural cholinergic mechanisms in the control of basal interdigestive pancreatic secretion in rats. In contrast, the pancreatic protein response to an intraduodenal meal depends on CCK, whereas fluid and HCO3- responses also depend on other hormonal factors. Our results suggest that a muscarinic (probably M3) mechanism can decrease the postprandial CCK release independently of the pancreatic feedback control by trypsin.

Animals↗
PubMed1990

Effect of selective sigma ligands on duodenal alkaline secretion in the rat.

The previous demonstration of sigma receptors localized in the mucosa and the submucosal plexus of the duodenum led us to investigate the activity of two specific sigma (sigma H) receptor ligands, di (ortho-tolyl) guanidine (DTG) and (+) N-allyl normetazocine (d-NANM) on the alkaline secretion of the duodenum in anesthetized rats. DTG (0.25-2 mg/kg, i.v.) and d-NANM (0.5-5 mg/kg, i.v.) induced a dose-related increase of bicarbonate output, from a basal level of 7.6 +/- 0.1 microEq/cm/hr to a stimulated plateau of 14.1 +/- 0.2 and 14.2 +/- 0.2 microEq/cm/hr, respectively, for the next 2 hr. In contrast, the venous injection of I-NANM (5 mg/kg) did not significantly stimulate duodenal bicarbonate output. Intravenous administration of naloxone (0.2 mg/kg) failed to modify the response to both DTG and d-NANM, whereas haloperidol (0.5 mg/kg, i.v.) abolished the response to both drugs. The response to DTG was unchanged after indomethacin (0.25 mg/kg), yohimbine (2 mg/kg), atropine (1 mg/kg), sulpiride (1 mg/kg) or SCH 23,390 (0.45 mg/kg), and partly decreased after prazosin (1 mg/kg). Hexamethonium (1 mg/kg), and tetrodotoxin (5 micrograms/kg) reduced the response to DTG, respectively, by 79% (P less than 0.01) and 91% (P less than 0.01), whereas bilateral vagotomy suppressed it. The cholecystokininA receptor antagonist (-)L364,718 decreased the response to DTG by 91% (P less than 0.01). None of the antagonists changed the basal bicarbonate output but vagotomy, which induced a 52% (P less than 0.01) decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Relative importance of cholecystokinin and cholinergic nerve mechanisms in the regulation of pancreatic secretion in rats].

Several substances modulate the function of pancreatic acinar cells in vitro through specific receptors. All of them may also act in vivo, but the relative importance of their effect under physiological conditions is highly variable. The aim of this study was to assess the respective participation of cholinergic nerves and cholecystokinin (CCK) in the interdigestive pancreatic exocrine secretion and in the pancreatic response to intragastric or intraduodenal nutrients. Unanesthetized rats, equipped with a semichronic (5 days) pancreatic fistula, were used. They received a test-meal in the stomach (42 kJ) or the duodenum (21 kJ), and were infused intravenously with an antagonist of muscarinic (atropine, pirenzepin), nicotinic (hexamethonium), or CCK (L364718, lorglumide, Boc-Tyr(SO3)-Nle-Gly-D-Trp-Nle-Asp-NH-CH2-CH2-C6H5) receptors. Basal interdigestive pancreatic exocrine secretion decreased significantly after atropine, pirenzepine or hexamethonium. Protein output decreased more (peak inhibition 60 to 80 percent according to the drugs, p less than 0.01 to p less than 0.001) than volume or bicarbonate output (peak inhibition 25 to 65 percent according to the drugs, p less than 0.05 to p less than 0.01). CCK antagonists did not change the interdigestive pancreatic secretion. The cumulated response to the intraduodenal meal did not change after hexamethonium or pirenzepin, but increased after atropine (by approximately 50 percent, p less than 0.001 for volume and bicarbonate output, and nearly 100 percent, p less than 0.05 for protein output). The CCK antagonists entirely suppressed the protein response to the intraduodenal meal, decreased the volume response by 70 percent (p less than 0.01), and the bicarbonate response by 50 percent (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Role of opioid peptides in intestinal motility].

Endogenous opioid peptides derive from three precursors: proenkephalin A, maturing into enkephalins, proenkephalin B, maturing into dynorphins, and proopiomelanocortin, maturing into beta-endorphin and non-opioid fragments. All these opioid peptides can be detected by immunocytochemical methods in many neurons intrinsic to the gut and in cerebral and medullary neurons. The involvement of opioid peptides in the control of intestinal motility is demonstrated by experiments using injection of exogenous peptides or analogues, administration of antagonists or inhibition of their in vivo degradation. However, the pattern of action of opioids on intestinal motility is complex, since stimulant and inhibitory effects may occur via the different mu, delta and kappa opioid receptors, on muscle cells or on nerves and at central or peripheral sites. On the whole, opioid peptides should be considered as important neurotransmitters. Their main function on gut motility seems to be the regulation of other stimulant and inhibitory neurons inputting to the muscle cells of the gut.

Animals↗
PubMed1989

Central and peripheral effects of prostaglandin E2 and enprostil on exocrine pancreatic secretion in rats.

Prostaglandin E2 (PGE2) has been reported to exert some centrally mediated effects on intestinal motility and secretion and on gastric secretion, but it is not known whether such central effects exist on pancreatic secretion. The central and peripheral effects of PGE2 and enprostil, a long-acting, potent PGE2 analogue, were studied in conscious and anesthetized rats fitted with pancreatic fistulae. In chronically implanted, conscious rats, PGE2 inhibited the secretion of fluid, bicarbonate, and total protein in the pancreatic juice, both after i.v. or intracerebroventricular (icv) injections. The maximal inhibition was similar after both injection procedures (about 45% for fluid and bicarbonate and 60% for protein), but the potency of PGE2 was three to 10 times greater by the icv than the i.v. route. Enprostil also inhibited pancreatic secretion in a dose-related way. The maximal inhibition was larger than after PGE2 injection (about 70% for fluid and bicarbonate and 90% for protein). The potency of enprostil was five to 10 times lower by the icv than by the i.v. route. The diversion of gastric secretion suppressed the effect of icv PGE2 on fluid and bicarbonate output but not on protein and did not change the effect of enprostil on all the variables of pancreatic secretion. Adrenergic antagonists did not suppress the effect of icv PGE2 or enprostil on pancreatic secretion. In anesthetized rats, i.v. PGE2 inhibited hormone-stimulated protein secretion but did not change fluid and bicarbonate output, while i.v. enprostil inhibited cholecystokinin-stimulated fluid, bicarbonate, and protein output in the pancreatic juice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Substance P: a peripheral inhibitor of gastric acid secretion in the rat].

The inhibition of some peptidases in the central nervous system induces a decrease in gastric acid secretion. The present experiments indicate that substance P is not likely a candidate to mediate this effect in rats. Substance P, indeed, potently inhibits gastric acid secretion, but this effect appears mainly peripheral.

Animals↗
PubMed1989

Total pancreatic insufficiency in pigs: a model to study intestinal enzymes and plasma levels of digestive hormones after pancreatic supplementation by a whole pancreas preparation.

Oral pancreatic enzyme replacement therapy generally benefits patients with severe pancreatic deficiency. However, the fate of oral pancreatic supplements in the digestive lumen and their possible effects on circulating gut hormones are only partially known. The purpose of this article is to validate an experimental model that produces total pancreatic insufficiency in pigs, and to study the fate of orally administered Eurobiol, a whole pancreas lyophilized preparation, and its effects on circulating plasma levels of five digestive hormones. Pancreatic insufficiency was created by pancreatic duct ligation, and the duodenal, jejunal and ileal contents were sampled through cannulas before a normal meal and 0.5-24 h later. Blood samples were taken at the same times, and plasma neurotensin, pancreatic polypeptide, secretin, cholecystokinin (CCK), and gastrin were measured. In pigs with pancreatic insufficiency, Eurobiol, given during the meal, induced a significant increase in all enzyme activities in the duodenum and the jejunum, and in the levels of amylase, trypsin, and chymotrypsin in the ileum, relative to placebo. In the duodenum, the peak concentrations of enzyme activities were 19, 11, 17, and 29% (p less than 0.001) of the postprandial peak activities measured in control pigs with an intact pancreas for lipase, amylase, trypsin, and chymotrypsin, respectively. In the jejunum, the same activities were, respectively, 30, 11, 25, and 36% (p less than 0.01-0.001) of normal peaks. In pigs with pancreatic insufficiency, basal and integrated meal-stimulated neurotensin levels were increased; basal, peak, and integrated meal-stimulated pancreatic polypeptide and secretin levels were increased, whereas gastrin and CCK were not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Thiorphan and acetorphan inhibit gastric secretion by a central, non-opioid mechanism in the rat.

Thiorphan and its prodrug, acetorphan, are two inhibitors of enkephalinase (EC 3.4.24.11), a membrane-bound peptidase which plays an important role in the metabolic degradation of enkephalins. Since exogenous opioids have been reported to both stimulate and inhibit gastric secretion, the effects of thiorphan and acetorphan were studied in conscious rats equipped with chronic gastric fistulas. While i.v. thiorphan had no effect, both i.c.v. thiorphan and i.v. acetorphan potently inhibited the basal gastric acid output and the acid output stimulated by pentagastrin. Conversely, neither drug affected the histamine- or methacholine-induced stimulation of acid secretion. Neither thiorphan or acetorphan had any effect on the acid secretion stimulated by a combination of pentagastrin and acetylcholine in vagotomized rats. The results strongly suggest that both drugs inhibit gastric secretion through an effect at the level of the central nervous system, which decreases the vagal drive to the stomach. However, the effects of thiorphan and acetorphan were not prevented by naloxone. This is at variance with most of the effects of these drugs reported to date, including the inhibition of gastric secretion in cats. Furthermore, these effects were observed at doses which could inhibit other enzymes apart from enkephalinase. This suggests that the antisecretory action in rats is related to the protection of some non-opioid peptide(s) from degradation. In conclusion, both peptidase inhibitors inhibit gastric secretion of the rat through a central mechanism involving unknown, non-opioid peptide(s).

Animals↗
PubMed1988

Effects of CRL 40827 and salbutamol on exocrine pancreatic secretion in rats.

The effects of the drug CRL 40827 and salbutamol, a structurally related compound, on exocrine pancreatic secretion in acutely fistulized anaesthetized rats and in chronically fistulized conscious rats were studied. CRL 40827 and salbutamol (0.05-0.45 mumol/kg per min, for 2 h) increased the basal secretion of fluid and bicarbonate in anaesthetized rats. The effect of CRL 40827 (15% of the maximal effect of secretin) was suppressed by propranolol (a non-specific beta-adrenoceptor antagonist), by ICI 118551 (a beta 2-antagonist) and by atenolol (a beta 1-antagonist). The effect of salbutamol (25% of the maximal effect of secretin) was suppressed by propranolol and ICI 118551 but was only slightly decreased by atenolol. The stimulant peak effects of CRL 40827 and salbutamol on volume and bicarbonate output were additive to those of 2-deoxy-glucose whereas the effect of 2-deoxy-glucose on protein output was not changed by either drug. CRL 40827 and salbutamol decreased the basal interdigestive protein output in a dose-related manner in conscious rats. CRL 40827 was 27 times less potent than salbutamol. The pancreatic outputs of fluid, bicarbonate and protein after an intragastric meal were decreased by both drugs. However, only salbutamol significantly decreased the cumulative effect of the meal on protein output compared to basal output. These results suggest that the stimulant effect of salbutamol on the pancreatic secretion of fluid and bicarbonate depends mainly on beta 2-adrenoceptors whereas that of CRL 40827 involves adrenoceptors of an as yet undefined subtype.

Adrenergic alpha-Agonists↗
PubMed1988

Central and peripheral inhibition of exocrine pancreatic secretion by alpha-2 adrenergic agonists in the rat.

The effect of ST91, a clonidine derivative crossing poorly the blood-brain barrier, was compared to that of clonidine on exocrine pancreatic secretion in rats. The experiments were performed in anaesthetized rats after stimulation by a maximal dose of 2-deoxy-D-glucose, and in conscious rats under basal interdigestive conditions. In anaesthetized rats, the 2-deoxy-D-glucose-induced stimulation of pancreatic secretion was suppressed by clonidine but not by ST91, both injected subcutaneously. This effect of clonidine was not antagonized by prazosin, but was decreased by 70-100% (according to the variables measured) by yohimbine. The alpha-2 antagonists rauwolscine and corynanthine were less efficient than yohimbine, while idazoxan suppressed totally the effect of clonidine. In conscious rats, the basal interdigestive secretion was inhibited by ST91 and by clonidine. After sc injections, the potency of ST91 was about ten times smaller than that of clonidine, whereas after injections in the cerebral ventricles, ST91 was as potent as clonidine to inhibit pancreatic secretion. Most (70-90%) of the inhibition induced by sc ST91 and clonidine in conscious rats was suppressed by yohimbine or by prazosin. It is concluded that both ST91 and clonidine inhibit pancreatic secretion in rats, and that this effect has probably both central and peripheral components. The central effect involves alpha-2 receptors, while the peripheral effect may involve alpha-1 and alpha-2 receptors.

Adrenergic alpha-Agonists↗
PubMed1988

[Tetracosactide (ACTH 1-24) stimulates the external pancreatic secretion by a vagal mechanism in the rat].

The use of ACTH has been recently proposed in the therapy of the withdrawal syndrome in opiate addicts. By analogy with previous results obtained with opiates and clonidine, we looked for a possible central effect of ACTH 1-24 (tetracosactide) on the nervous pathways controlling the external pancreatic secretion in the rat. Tetracosactide displayed a central, vagally mediated, stimulant effect on the external pancreatic secretion, at variance with opiates and clonidine, which displayed central inhibitory effects in the same model. These results suggest that tetracosactide has a mechanism of action different from clonidine.

Animals↗
PubMed1987

Intrinsic nerves of the pancreas after celiac and superior mesenteric ganglionectomy in rats: a morphologic study of acetylcholinesterase activity and catecholamine histofluorescence.

The effect of surgical celiac and superior mesenteric ganglionectomy (GGX) on intrinsic pancreatic innervation was studied in male Wistar rats. Neurons were stained in the pancreas of control and ganglionectomized rats with histochemical methods evidencing the acetylcholinesterase (AChE) activity and the induced fluorescence of catecholamines. Two segments of the head of the pancreas ("duodenal" and "splenic" segments) were studied. The surface density of neuronal cell bodies was larger in the splenic segment than in the duodenal segment of the head of the pancreas (p less than 0.01), both in control and in ganglionectomized rats. The surface density of the neuronal cell bodies and the intensity of AChE staining were not significantly different in control and in ganglionectomized rats. Most AChE-positive fibers survived after ganglionectomy; only some of them disappeared. These disappearing fibers corresponded to the thinnest fiber bundles found in the pancreatic tissue of control rats. Only 10% of catecholamine fibers remained after ganglionectomy. Some of the remaining fibers may run through direct duodenopancreatic pathways.

Acetylcholinesterase↗
PubMed1987

Effect of modafinil on pancreatic exocrine secretion in rats. A comparison with adrafinil and related drugs.

The effects of modafinil and adrafinil, 2 drugs that induce locomotor hyperactivity, and those of the parent compounds CRL 40467 and CRL 40385, were studied on the external pancreatic secretion of anaesthetized and conscious rats. In anaesthetized rats modafinil, adrafinil, and CRL 40385 antagonized the central vagal stimulation of protein output induced by 2-deoxy-D-glucose in the pancreatic juice. In conscious rats, modafinil and adrafinil inhibited the output of protein in the basal interdigestive pancreatic secretion. Modafinil was more active than adrafinil as an inhibitor of pancreatic secretion. The effects of modafinil and adrafinil were different from those of sympathetic amines and dopamine: they did not stimulate the output of bicarbonate in anaesthetized rats, and pancreatic inhibition observed in conscious rats was not inhibited by either yohimbine or prazosin.

Anesthesia↗
PubMed1987

Cholinergic mechanisms in the pancreas after extrinsic denervation in the rat.

Extrinsic denervations of the pancreas were carried out in rats using bilateral truncal abdominal vagotomy and/or celiac and superior mesenteric ganglionectomy. Chronic fistulas were produced and pancreatic secretion was then measured in conscious animals. In all three groups of extrinsically denervated animals the basal pancreatic secretion was significantly decreased by 15-44% (fluid), 32-59% (bicarbonate output), and 33-43% (protein output). Meal-stimulated secretion was decreased in denervated animals by 38-57% (fluid), 32-44% (bicarbonate output), and 36-64% (protein output). In extrinsically denervated rats, atropine inhibited basal pancreatic fluid by 26-38%, bicarbonate output by 46-71%, and protein output by 63-80%, whereas hexamethonium inhibited basal protein output by 36-58%. These data indicate that cholinergic mechanisms persist in the pancreas after extrinsic denervation. This may correspond either to the spontaneous activity of intrapancreatic excitatory cholinergic neurons or to the drive of these neurons by preganglionic fibers running through nonclassic (such as duodenopancreatic) pathways. No important difference was observed between the effects of vagotomy and those of celiac and superior mesenteric ganglionectomy, indicating that most of the excitatory vagal fibers for the exocrine pancreas run through the celiac pathway and that adrenergic fibers had little effect on the conditions tested.

Animals↗
PubMed1987

Effects of morphine on gastric ulceration, barrier mucus and acid secretion in pylorus-ligated rats.

The effects of intraperitoneal (IP) or intracerebroventricular (ICV) administration of morphine on acid and pepsin secretion, gastric ulceration and gastric bound mucoproteins were investigated in pylorus-ligated rats. Morphine, administered IP, produced a dose-dependent inhibition of the gastric secretion volume, acidity, pepsin output and bound mucoproteins. By contrast, the effect of morphine on gastric ulcers was not dose-dependent: a significant increase in gastric lesions was obtained with morphine 5 mg/kg IP. Naloxone IP prevented the effects of morphine on gastric secretory volume, acidity and pepsin output, but not on gastric mucus and ulcer score. ICV administration of morphine induced a dose-dependent inhibition of secretory volume, acidity and ulcer score, whereas no modification of gastric mucus was observed. Naloxone ICV prevented the effects of ICV morphine. Overall results suggest that morphine inhibits gastric secretion through both central and peripheral opioid receptors, whereas the inhibitory effect of morphine on bound mucus appears to be exerted on mucus synthesis through peripheral opioid receptors. This inhibitory effect on barrier mucus accounts at least in part for the gastric ulcerogenic action of morphine.

Animals↗