Pituitary adenylate cyclase-activating peptide is a potent modulator of human colonic motility.
Pituitary adenylate cyclase-activating peptide (PACAP) represents a novel brain-gut peptide with high sequence homology to vasoactive intestinal polypeptide (VIP). Since PACAP has been identified in the human gut, the effect of the two molecular forms PACAP-(1-38) and PACAP-(1-27), the hybrid PACAP-(1-23)VIP-(24-28), and VIP on the contractility of the longitudinal muscle of human sigmoid colon was tested in vitro. All peptides inhibited the spontaneous phasic contractions and relaxed concentration-dependently carbachol-precontracted preparations. The effects of the peptides remained unaffected by tetrodotoxin, by inhibition of phosphodiesterase activity, and by inhibition of nitric oxide synthesis. Apamin reduced only the effects of the PACAP peptides, whereas tetraethylammonium blocked only the effect of VIP. In conclusion, PACAP peptides and VIP mediate their relaxant effects via activation of specific PACAP and VIP receptors coupled to different potassium channels.
Schwörer
H
H
Dept. of Medicine, University of Göttingen, Germany.
Clemens
A
A
Katsoulis
S
S
Köhler
H
H
Creutzfeldt
W
W
Schmidt
W E
WE
D015761:4-Aminopyridine / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D012809:Colon, Sigmoid / Q000187:drug effects / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D015221:Potassium Channels / Q000187:drug effects; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D010726:Phosphodiesterase Inhibitors; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019335:Nitroarginine; D001030:Apamin; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D002217:Carbachol; D001120:Arginine; D015761:4-Aminopyridine