Effect of Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide on Pancreatic, Hepatic and Duodenal Mucosal Bicarbonate Secretion in the Pig

Abstract

Background and Method: The potency of pituitary adenylate cyclase-activating polypeptide (PACAP) and the related vasoactive intestinal peptide (VIP) on pancreaticobiliary and duodenal mucosal bicarbonate secretion (DMBS) was studied in anaesthetized pigs. VIP, PACAP27 and PACAP38 were infused at doses of 250, 500, 1,000, 2,000 and 6,000 pmol/kg·h. Results: Infusion of VIP in these concentrations increased the portal plasma concentrations of VIP from 9 to 102, 220, 600, 850 and 3,795 pM, respectively. At doses of 1,000 and 6,000 pmol/kg·h all three peptides significantly stimulated pancreatic bicarbonate secretion, VIP from 0.0 to 0.3 and 7.6 mmol/h, PACAP27 from 0.0 to 2.3 and 8.2 mmol/h, and PACAP38 from 0.0 to 0.2 and 7.4 mmol/h, respectively. Only during infusion of 6,000 pmol/kg·h did the three peptides elicit a significant increase in hepatic bicarbonate output. At this dose VIP increased hepatic bicarbonate output from 0.4 to 3.8 mmol/h, PACAP27 from 0.3 to 3.6 mmol/h, and PACAP38 from 0.1 to 1.4 mmol/h, respectively. Infusion of VIP (500, 1,000, 2,000 and 6,000 pmol/kg·h) dose-dependently and significantly enlarged DMBS from 0.09 to 0.19, 0.41, 0.54 and 0.53 mmol/h, respectively. A significant effect of PACAP27 and PACAP38 on DMBS was only obtained at a dose of 6,000 pmol/kg·h, and at this dose VIP-induced DMBS was 4- and 8-fold higher than that induced by PACAP27 and PACAP38, respectively. Conclusions: VIP, PACAP27 and PACAP38 all have a pharmacological effect on both DMBS and pancreaticobiliary bicarbonate secretion. When comparing these results with the distribution of VIP/PACAP neurons and relevant receptors, it seems likely that VIP and PACAP have a physiological importance as neurotransmitters in the pancreas and duodenum, but not in the liver. The differences in the effect of VIP and PACAP on DMBS observed in this study indicate that there are variations between pancreatic and duodenal PACAP/VIP receptor subtypes, or that the duodenal inactivation of the peptides is different from the inactivation in the pancreas.

Characterisation of CART-containing neurons and cells in the porcine pancreas, gastro-intestinal tract, adrenal and thyroid glands

“…CART resided also in VIP containing fibers innervating the Brunner glands and the gut mucosa. Since VIP is a well established gut secretagogue [50], a role for CART in modulation of VIP mediated secretory functions cannot be excluded.…”

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).…”

Effects of PACAP on Oxidative Stress-Induced Cell Death in Rat Kidney and Human Hepatocyte Cells

“…PACAP stimulates glucose output from perfused rat liver (Yokota et al 1995) and also in vivo (Sekiguchi et al 1994). PACAP infusion elicited a significant increase in hepatic bicarbonate output in the pig, though only at pharmacological doses, suggesting that PACAP does not play a physiological role in this process (Glad et al 2003). It has also been demonstrated that PACAP induces expression of corticosteroid-binding globulin in cultured fetal hepatocytes (El Fahime et al 1996).…”