Enhancement by atropine of the pancreatic exocrine secretions evoked by vagal stimulation in the pithed rat.

Abstract

SUMMARY1. Pancreatic secretions were collected in response to 15 min periods of bilateral stimulation of the cervical vagus nerves in the pithed rat.2. The weight of juice, total HC03-and total protein evoked by a second period of vagal stimulation were essentially similar to those of the first period of vagal stimulation.3. When the second period of vagal stimulation was preceded by an intravenous bolus injection of atropine sufficient to block the vagally induced bradycardia, the weight of secretion and total protein were greatly potentiated over an extended time course far exceeding that of the period of vagal stimulation. Total HC03-was unchanged.4. By contrast, atropine was effective in antagonizing the stimulatory effects of the muscarinic agonist methacholine injected intravenously.5. The putative VIP (vasoactive intestinal polypeptide) antagonist [D-p-chloroPhe6, Leul7]-VIP injected intravenously also increased the vagally evoked weight of juice, with total HCO,3-and total protein unchanged. This was explicable by a partial agonist effect which was additive to the stimulatory action of vagal stimulation.6. To explain these results, it is proposed that endogenously released acetylcholine exerts a negative feedback effect on the postganglionic varicosities which release both acetylcholine and another cotransmitter which was not excluded as being VIP. In the presence of atropine, the cotransmitter is proposed to be released from the inhibitory feedback, thus enhancing the response to vagal stimulation.

An investigation into the relative merits of pituitary adenylate cyclase‐activating polypeptide (PACAP‐27) and vasoactive intestinal polypeptide as vagal neuro‐transmitters in exocrine pancreas of rats

“…This has been shown to block the erectile response in sexually active rats and to inhibit VIP binding in glial cell cultures (Gozes et al 1989). On the basis of our previous experiences (Barrett et al 1993) In each animal the following procedures were undertaken: tracheostomy, cannulation of the carotid artery for recording of arterial blood pressure, cannulation of the jugular vein for slow bolus injection of drugs, ligation of the pyloro-duodenal junction to prevent entry of gastric acid, ligation of the pancreatic-bile duct above the pancreas to prevent the flow of bile, and cannulation of the pancreatic duct at its entrance to the duodenum for the collection of' pancreatic secretions.…”

“…These studies indicate that, as well as acetylcholine, an atropine-resistant vagal neurotransmitter is released which evokes the serous secretion. The position in the rat has proved to be more complicated in that atropine markedly potentiated the vagally evoked pancreatic secretions (Barrett, McDougall & Morrison, 1993), from which it was inferred that acetylcholine, released from vagal varicosities, exerted inhibitory feedback on the release of a second vagal neurotransmitter.…”

“…Previously, an investigation of the putative competitive antagonist [D-p-chloroPhe6,Leu'7]-VIP (Pandol, Dharmsathaphorn, Schoeffield, Vale & Rivier, 1986) was unsuccessful since this compound was shown to have an agonist action which summated with the stimulatory effects of vagal stimulation (Barrett et al 1993). Another putative antagonist, [Lys',Pro25,Arg3'4,Tyr6]-VIP (abbreviated as VIPi), is a hybrid of VIP, which causes relaxation of smooth muscle, and neurotensin, which causes contraction of smooth muscle (Gozes, Meltzer, Rubinrout, Brenneman & Fridkin, 1989).…”

“…HCO3-was assayed by back titration with NaOH after addition of excess HCl and protein was assayed as the absorbance at 280 nm (Barrett et al 1993). …”

GI Tract

“…both differences were abolished. As in the rat (Barrett et al 1993), the flow of pancreatic juice during continuous stimulation was augmented (9'3 ± 2'2 ,ul min -I (g glandrl; P < 0'05) to approximate that during intermittent stimulation at the corresponding frequency (10'7 ± 1'9,u1 min-I (g glandr l ). In contrast, the enhanced output of protein during intermittent stimulation was substantially reduced (22 ± 11 cf.…”