Pituitary adenylate cyclase activating polypeptides, PACAP-27 and PACAP-38: stimulators of electrogenic ion secretion in the rat small intestine.
1. The effects of pituitary adenylate cyclase activating polypeptide (PACAP)-27 and PACAP-38 were investigated and compared with vasoactive intestinal polypeptide (VIP) responses in voltage clamped preparations of rat jejunum. Under these conditions electrogenic ion secretion was continuously recorded. 2. PACAP-27 is the most potent secretagogue described thus far, exhibiting a concentration-dependent dual secretory action. At low concentrations it stimulated rapid, transient secretory responses (not seen with either PACAP-38 or VIP) and these were inhibited by tetrodotoxin (TTX). At higher nM concentrations of PACAP-27 more prolonged secretory responses predominated which were insensitive to TTX. 3. In the presence of TTX, the concentration-response curve to PACAP-27 gave an EC50 value of 29.4 +/- 5.4 nM (n = 4) compared with 0.8 +/- 0.1 nM (n = 9) for PACAP-27 alone and 30.6 +/- 5.6 nM (n = 5) for PACAP-38. C-terminal fragments of PACAP-38 were not significantly effective. 4. Blockade of muscarinic and nicotinic receptors partially inhibited the low concentration effects of PACAP-27. Substance P desensitization and capsaicin pretreatment were effective at inhibiting the transient secretory PACAP-27 responses. Evidence is presented for selective, high affinity PACAP-27 receptors on submucous neurones innervating the mucosal region of the rat jejunum.
Cox
H M
HM
Department of Pharmacology, University of Cambridge.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000494:pharmacology*; D010451:Peptide PHI / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010902:Pituitary Gland / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D010451:Peptide PHI; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases