Effect of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide on pancreatic, hepatic and duodenal mucosal bicarbonate secretion in the pig.
METHODS
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 x 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.
Department of Medical Gastroenterology, Odense University Hospital, Odense University, Odense, Denmark. glad@dadlnet.dk
Henrik
H
Glad
Mark A
MA
Ainsworth
Per
P
Svendsen
Jan
J
Fahrenkrug
Ove B
OB
Schaffalitzky de Muckadell
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010189:Pancreatic Juice / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013552:Swine; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D001639:Bicarbonates; D005765:Gastrointestinal Agents; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide