Pituitary adenylate cyclase activating peptide, a novel VIP-like gut-brain peptide, relaxes the guinea-pig taenia caeci via apamin-sensitive potassium channels

Abstract

Effects of pituitary adenylate cyclase activating peptide (PACAP-(1-27)) and vasoactive intestinal polypeptide (VIP) on the guinea-pig taenia caeci were studied in the presence of guanethidine and scopolamine. Both peptides (1 nmol/1-1 mumol/l) concentration-dependently relaxed the smooth muscle of the taenia. PACAP-(1-27) and VIP were nearly equipotent. Apamin (30 nmol/l), a selective blocker of calcium-activated potassium channels, abolished the relaxation induced by PACAP-(1-27) whereas the effect of VIP remained unaffected. PACAP-(1-27) may be a candidate for the noncholinergic, non-adrenergic inhibitory neurotransmitter which induces apamin-sensitive relaxation in the intestinal tract.

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…PACAP also exerts a relaxant effect on intestinal smooth muscles from rat (Mungan et al, 1992a;Schwörer et al, 1992;Katsoulis et al, 1993b;Grider et al, 1994;Ekblad and Sundler, 1997;Olsson and Holmgren, 2000), guinea pig (Mungan et al, 1992a;Schwörer et al, 1992;Katsoulis et al, 1993b;Grider et al, 1994;Ekblad and Sundler, 1997;Olsson and Holmgren, 2000) and Atlantic cod, Gadus morhua (Mungan et al, 1992a;Schwörer et al, 1992;Katsoulis et al, 1993b;Grider et al, 1994;Ekblad and Sundler, 1997;Olsson and Holmgren, 2000), thus reducing the motility of the bowel (Lä uff et al, 1999). The mechanism by which PACAP induces muscle relaxation along the gastrointestinal tract has been extensively studied.…”

Junctional Transmissions in Smooth Muscle of the Guinea Pig Duodenum and Their Modulation by the Prokinetic Agent DQ-2511

“…The present experiments did not investigate further the mediator of this i.j.p., but in many tissues some substances such as adenosine triphosphate [23], vasoactive intestinal peptide [24], or pituitary adenylate cyclase activating polypeptide [25,26] are candidate mediators of this potential. Possible involvement of nitric oxide in the i.j.p.…”

Impact of caveolin-1 knockout on NANC relaxation in circular muscles of the mouse small intestine compared with longitudinal muscles

“…They mediate most of the inhibitory responses in the gastrointestinal tract (GIT) and control many physiological reflexes, e.g., relaxation of the lower esophageal sphincter after swallowing, receptive relaxation of the proximal stomach during eating, and descending inhibition in response to distention (44). NANC neurotransmitters include nitric oxide (NO) (5,44), ATP (6,55), vasoactive intestinal peptide (VIP) (24), pituitary adenylate cyclase-activating peptide (PACAP) (47), and carbon monoxide (37).…”

“…In smooth muscle and interstitial cells of Cajal (ICC), the most important caveolin is cav1 (12,14). They form homo-and heterooligomers that insert in the inner leaflet of plasma membrane to form the characteristic flask-shaped caveolae (47). These membrane invaginations serve as membrane-organizing centers.…”