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Am J Physiol Gastrointest Liver Physiol 272: G1433-G1438, 1997;
0193-1857/97 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 6 1433-G1438, Copyright © 1997 by American Physiological Society

ARTICLES

Dual effects of PACAP on guinea pig gallbladder muscle via PACAP-preferring and VIP/PACAP-preferring receptors

H. P. Parkman, A. P. Pagano and J. P. Ryan
Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.

The aims of this study were to determine the effect and mechanism of action of pituitary adenylate cyclase-activating peptide (PACAP) on gallbladder muscle. Guinea pig gallbladder muscle strips were studied isometrically. In noncontracted muscle strips, PACAP-27 and PACAP-38 caused dose-dependent contractions, whereas vasoactive intestinal peptide (VIP) caused dose-dependent relaxation. PACAP-27 contractions were resistant to tetrodotoxin, atropine, and the substance P receptor antagonist [D-Arg1,D-Trp7,9,Leu11]substance P (Spantide) but were inhibited by the selective PACAP receptor antagonist PACAP-(6-38) and slightly increased with the VIP receptor antagonist [4-chloro-D-Phe6,Leu17]VIP. In cholecystokinin-precontracted muscle strips, both VIP and PACAP caused relaxations. This relaxant effect of PACAP-27 was inhibited by PACAP-(6-38) and [4-chloro-D-Phe6,Leu17]VIP, but not by tetrodotoxin. These studies suggest that PACAP has dual excitatory and inhibitory effects on guinea pig gallbladder muscle. The contractile effect of PACAP is a direct action on muscle through PACAP-preferring receptors. The relaxant effect of PACAP is seen in precontracted muscle strips and mediated through VIP/ PACAP-preferring receptors.


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