Comparative study of vascular relaxation and receptor binding by PACAP and VIP

The pharmacological properties of the pituitary adenylate cyclase activating peptides (PACAPs) and vasoactive intestinal peptide (VIP) were compared using: (i) relaxation of vascular and gastric smooth muscle in vitro, and (ii) radioligand binding to membrane preparations of a variety of tissues. Vasoactive intestinal peptide and PACAP-27 were similarly potent in relaxing rat mesenteric arteries, porcine coronary arteries, and rat gastric smooth muscle, whereas PACAP-38 was either more or less potent than the other two peptides depending on the tissue model. Cross-desensitization to relaxation and radioligand binding studies of porcine coronary arteries suggested that VIP and the PACAPs interact with a common receptor in this tissue. A PACAP-preferring receptor with low affinity for VIP was identified in radioligand binding studies of rat brain and anterior pituitary. A second, nonselective, receptor that binds VIP and both PACAPs with high affinity was observed in preparations of rat and porcine arteries and rat lung, liver, brain, and anterior pituitary.