Pituitary adenylate cyclase activating polypeptide (PACAP) redistributes the blood within the pancreas of anesthetized rats.
The aim of the study was to evaluate the effects of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) on splanchnic blood flow in anesthetized rats. For this purpose, either PACAP-38 dissolved in saline or saline alone was injected intravenously 5 (10 nmol/kg body weight (bw) PACAP-38) and 30 min (5 or 10 nmol/kg) before measurements. The blood flow to the whole pancreas, islets, duodenum and colon was then measured with a microsphere technique. The higher dose of PACAP-38 slightly increased blood glucose concentrations at both 5 and 30 min after administration, whereas the lower had no effect. Both doses of PACAP-38 induced a transient initial decrease in mean arterial blood pressure. The lower dose of PACAP-38 decreased fractional islet blood flow 30 min after administration, but did not affect the other blood flows. The higher dose of the peptide (10 nmol/kg bw) caused an increase in whole pancreatic blood flow at both 5 and 30 min after administration, whereas islet blood flow was only increased at the former time. At both time points PACAP-38 redistributed the blood flow within the pancreas in favour of the exocrine pancreas. This resulted in a decreased fractional islet blood flow, i.e., the fraction of whole pancreatic blood flow diverted through the islets. At 5 min after PACAP-38 administration duodenal blood flow was decreased, whereas after 30 min no effects on duodenal or colonic blood flow were observed. Administration of a VIP antagonist intravenously (20 nmol/kg bw) decreased the PACAP-38-induced pancreatic blood flow increase and intrapancreatic redistribution. When only the VIP antagonist was given both pancreatic and islet blood decreased in concert. It is concluded that administration of PACAP-38 induces a blood flow increase in the pancreas, preferably in the exocrine parts of the gland, by actions mediated by PACAP-38 receptors shared with VIP.
Carlsson
P O
PO
Department of Medical Cell Biology, Uppsala University, Sweden.
Ostenson
C G
CG
Efendic
S
S
Langel
U
U
Jansson
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010902:Pituitary Gland / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D001786:Blood Glucose; D009479:Neuropeptides; D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014665:Vasodilator Agents; D014660:Vasoactive Intestinal Peptide