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

Abstract

SUMMARYPancreatic exocrine secretions were collected over 15 min periods and analysed in terms of weight of juice, total HCO3-and total protein in anaesthetized and pithed rats. Pituitary adenylate cyclase-activating polypeptide (PACAP) (i.v.) evoked a serous HCO3-secretion which contained relatively little protein, together with a marked vasodepressor action. The latter was still maximal at lower doses of PACAP, which evoked diminished pancreatic secretions. The effects of PACAP were similar to those evoked by the same dose of VIP and by cervical vagal stimulation, while secretin evoked a much larger secretion of fluid and HCO3-. The time courses of the PACAPevoked secretions were significantly delayed compared with those of VIP. In the pithed rat, PACAP caused the same level of pancreatic secretions as in the anaesthetized rat, though this was now accompanied by a substantial pressor response which was blocked by phentolamine or prazosin, indicating that it was a -adrenoceptor mediated. VIP caused a depressor response in the pithed rat, as well as the same level of pancreatic secretions as in the anaesthetized rat. The putative VIP antagonist [Lys',Pro25,Arg3'4,Tyr6]-VIP (abbreviated as VIPi) caused a selective and significant reduction in the HCO3-secretion evoked by VIP and blocked the vasodepressor response caused by VIP. By contrast, VIPi did not antagonize either the secretory or vasodepressor actions of PACAP. Unilateral electrical stimulation of the cervical vagus nerve evoked significant increases in the weight of juice, total protein and total HC03-secreted. When preceded by injection of VIPi, vagally evoked secretions were unchanged in terms of weight of juice and total protein but had a significantly reduced HCO3 content. These results are consistent with the release of VIP, though not PACAP, as a vagal neurotransmitter in the exocrine pancreas.

Pituitary adenylate cyclase-activating polypeptide in intrinsic and extrinsic nerves of the rat pancreas

“…PACAP is known to stimulate both exocrine and endocrine secretion and regulate blood flow (Alonso et al 1994;Fridolf et al 1992;Kashimura et al 1993;Tornoe et al 1996Tornoe et al , 1997Yada et al 1994Yada et al , 1996Yokota et al 1993;Wheeler et al 1997). PACAP is known to stimulate both exocrine and endocrine secretion and regulate blood flow (Alonso et al 1994;Fridolf et al 1992;Kashimura et al 1993;Tornoe et al 1996Tornoe et al , 1997Yada et al 1994Yada et al , 1996Yokota et al 1993;Wheeler et al 1997).…”

“…Intravenous and intra-arterial infusion of PACAP and VIP equipotentially increase the exocrine secretion of pancreatic juice, bicarbonate and protein during atropine blockade (Alonso et al 1994;Tornoe et al 1996Tornoe et al , 1997Wheeler et al 1997;Zabielski et al 1994), suggesting that VPAC 1 and VPAC 2 receptors are responsible for these effects. Infused PACAP dose-dependently stimulates insulin (Fridolf et al 1992;Tornoe et al 1996Tornoe et al , 1997, glucagon (Fridolf et al 1992;Tornoe et al 1996Tornoe et al , 1997 and somatostatin secretion (Tornoe et al 1996).…”

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…Intravenous injection of PACAP triggers amylase (Mungan et al, 1991;Alonso et al, 1994), pancreatic fluid, bicarbonate, and protein secretions (Naruse et al, 1992;Alonso et al, 1994;Zabielski et al, 1994;Rodríguez-López et al, 1995;Onaga et al, 1996;Wheeler et al, 1997;Lee et al, 1998;Glad et al, 2003). PACAP also induces vasodilation and increases pancreatic blood flow, notably in the exocrine part of the gland (Carlsson et al, 1996;Ito et al, 1998).…”

Control of Glucose Homeostasis by Incretin Hormones

“…53 The biological actions of PACAP appear to be very broad and diverse. They include stimulation of glucagon, somatostatin and insulin secretion, 53 increase of pancreatic exocrine juice flow, 54 and regulation of gastrointestinal motility. 55 The insulinotropic effect of PACAP, which is glucose-dependent, is mediated by stimulation of cyclic adenosine monophosphate (cAMP) formation and involves an increase in intracellular calcium .…”