The pharmacological properties of the pituitary adenylate cyclase acti
vating 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 var
iety of tissues. Vasoactive intestinal peptide and PACAP-27 were simil
arly potent in relaxing rat mesenteric arteries, porcine coronary arte
ries, and rat gastric smooth muscle, whereas PACAP-38 was either more
or less potent than the other two peptides depending on the tissue mod
el. Cross-desensitization to relaxation and radioligand binding studie
s of porcine coronary arteries suggested that VIP and the PACAPs inter
act with a common receptor in this tissue. A PACAP-preferring receptor
with low affinity for VIP was identified in radioligand binding studi
es of rat brain and anterior pituitary. A second, nonselective, recept
or that binds VIP and both PACAPs with high affinity was observed in p
reparations of rat and porcine arteries and rat lung, liver, brain, an
d anterior pituitary.