The stimulatory effects and binding characteristics of PACAP27 in rat dispersed pancreatic acini.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a recently isolated active peptide of the VIP (vasoactive intestinal peptide) family. Two bioactive forms, PACAP38 and PACAP27, a shorter N-terminal amidated peptide of PACAP38, have been identified. In this study, we explored the action of PACAP27 in rat dispersed pancreatic acini and the characteristics of its binding sites. PACAP27 stimulated amylase secretion and intracellular cAMP production in a dose-dependent manner. Adding 0.5 mM IBMX increased the potency of PACAP27 on the amylase secretion, but did not change the efficacy. The biological action of PACAP27 was mediated via intracellular cAMP as is also the case with PACAP38 or VIP. The time course study, however, revealed that PACAP stimulated the initial amylase secretion greater than VIP, suggesting an involvement of mechanisms other than intracellular cAMP. Binding studies using 125I-PACAP27 and 125I-VIP indicated that the binding sites for PACAP27 interacted with PACAP27 and VIP with a similar affinity. These observations suggested the presence of type II PACAP-binding sites in the normal acini of the rat pancreas which may be functionally coupled with acinar enzyme secretion.
Kashimura
J
J
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Shimosegawa
T
T
Iguchi
K
K
Mochizuki
T
T
Yanaihara
N
N
Koizumi
M
M
Toyota
T
T
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D008297:Male; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D000681:Amylases; D015056:1-Methyl-3-isobutylxanthine