[Action of diazepam on biliary secretion in the rat (author's transl)].
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Biomedical subjects
Publications and source records attributed to J Chariot.
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The effect os somatostatin (SS) and of its analogs D Trp 8-SS and Asn 5-SS was studied upon the external pancreatic secretion of the Rat after stimulation by 2 deoxy-D-glucose. The secretion of sodium and bicarbonate was similarly inhibited by all four peptides. The analog D Trp 8-SS was more effective in inhibiting pancreatic protein excretion.
The effects of methadone on pancreatic exocrine secretions in the rat were tested under basal conditions and after hormonal stimulation by secretin and caerulein or after stimulation of the differentially acting cholinergic agents acetylcholine, 2-deoxyglucose, and electrical stimulation of the vagus. Methadone had no effect on basal hydroelectrolytic secretion. It decreased basal enzyme secretion very slightly under our experimental conditions. The stimulatory effects of 75 mg of 2-deoxyglucose per kg were completely blocked by methadone at 5 mg per kg and this blockade was reversed by nalorphine at 6 to 9 mg per kg. It was found that there are doses of methadone (100 microgram) which block 2-deoxyglucose effects when injected into brain ventricles but are ineffective when systemically introduced. The effects of secretin, caerulein, acetylcholine, and electrical stimulation of the vagus were not depressed by methadone. These results strongly suggest that the methadone blockade of 2-deoxyglucose effects occurs at a central level and is mediated by narcotic drug receptors.
The effects of somatostatin on the secretions of the exocrine pancreas were studied in anesthetized and conscious fistula rats. Somatostatin resulted in a dose-dependent decrease of basal secretion (flow, bicarbonate, protein) in conscious rats. In anesthetized rats, basal secretion was initially augmented by bolus injections of 10 to 50 microgram per kg and was subsequently decreased by venous infusions of somatostatin at 1.5 to 100 microgram.kg-1.hr-1. This inhibition, which was poorly dose dependent, was greater for protein secretion than for that of water and electrolytes. Somatostatin inhibited caerulein-stimulated protein secretion by 40 to 50% but had no effect on secretion stimulated by exogenous and endogenous secretin. Somatostatin markedly inhibited secretion stimulated by 2-deoxyglucose and by electrical stimulation of the vagus nerves in a dose-dependent fashion (protein and bicarbonate exhibited a maximal inhibition of 85%). Acetylcholine-stimulated secretion was also inhibited by somatostatin, but the maximal inhibitions observed were only 505 for protein and 60% for bicarbonate. These findings agree with the hypothesis that somatostatin infusion leads to both a decrease of acetylcholine release at nerve endings and to a direct inhibition at the level of pancreatic effector cells.
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Male Wistar rats, fed a standard normal laboratory diet, drank ad libitum a 20% ethanol solution for 3 months. Basal and 2-deoxy-D-glucose (2DG) stimulated pancreatic secretion were measured. Basal secretion of sodium (-30%, p less than 0.001), bicarbonate (-35%, p less than 0.001) and total protein (-35%, p less than 0.001) were depressed in alcoholic versus control rats. Pancreatic response was identical in both groups with the smaller dose of 2DG, dose related in controls, and identical for both doses in alcohol-fed rats. The response was thus significantly smaller in alcohol-fed rats than in controls for the larger dose of 2DG (p less than 0.01). Pancreatic concentration and contents of amylase, trypsinogen, chymotrypsinogen and lipase were all decreased in alcoholic versus control rats (40-60%, p less than 0.001). These results are consistent with the hypothesis of functional modifications in pancreatic cholinergic innervation in alcohol-fed rats.
Miniature pigs were chronically implanted with gastric electrodes, strain gauge devices allowing the measurement of circular contractions in the antrum and body of the stomach, and with a duodenal catheter through which duodenal infusions were administered. Inhibition of gastric motility by intraduodenal agents was measured before and after truncal vagotomy in conscious animals 20 min after feeding of a normal meal. The agents infused in the duodenum (10 ml/min, 4 min), were: HCl 75 mEq/l(A), glucose 100 g/l(G), olive oil 10% pH 7(L), amino acids (AA) and saline. Before vagotomy, motor activity during the first 5 min was inhibited 50-80% with respect to basal levels; the duration of action was G No. L greater than A; AA had very little effect, and saline no effect. Inhibition was on the whole similar in the antrum and gastric body. After vagotomy, the inhibitory effect of A was reduced from 80 to 20% in the antrum, and completely suppressed in the gastric body. Inhibitory effects of G and L were completely suppressed.
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The stimulatory effects of isoproterenol and secretin on external pancreatic secretion were compared in the rat. 1. In acute fistula, pylorus ligation, atropine, glucagon did not change either of the stimulated secretions. Propranolol inhibited isoproterenol-induced secretion and did not change secretin induced stimulation. Theophylline alone displayed a large hydrelatic stimulatory effect, without increasing protein excretion; the effect of theophylline was additive with the effects of isoproterenol or secretin but no evidence was found of potentiation or prolongation of action. Isoproterenol did not increase pancreatic blood flow and induced no variations in the plasma levels of immunoreactive secretin. Combining various doses of isoproterenol and secretin did not allow to reach secretory levels greater than the maximal response to secretin. 2. In conscious rats chronic fistulae, isoproterenol and secretin had a distinct effect.
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Two types of pancreatic fistulas were directly compared in Wistar rats, to define more accurately the differences between collecting pancreatic juice under anesthesia (acute fistula) and in awake restrained animals (chronic fistula). Basal outputs of water, bicarbonate and total protein were about then times larger in chronic than in acute animals; they could be larger than the maximal secretory rate in anaesthetized rats. As a corollary, the chronic preparation was less sensitive to ecbolic and hydrelatic stimulations, with respect to basal levels. It is concluded that chronic fistula rats display a highly stimulated state of pancreatic secretion, probably due to the potentiation of several neurohumoral factors. Whatever this stimulation originates from, it renders the model less suitable for studies on ancreatic stimulating agents. On the contrary, anaesthetized rats displayed a low secretion more responsive to stimulating agents.
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