RECEPTORS FOR PITUITARY ADENYLATE CYCLASE-ACTIVATING PEPTIDE IN HUMAN LIVER

The presence as well as the pharmacological, molecular, and functional properties of pituitary adenylate cyclase-activating peptide (PACAP) receptors have been analyzed in human liver membranes compared in parallel with vasoactive intestinal peptide (VIP) receptors. [I-125]PACAP-27 bound to two classes of receptors with high [dissociation constant (K-d) = 0.47 nmol/L] and low (K-d = 8.0 nmol/L) affinities that represented about 34% and 66% of total binding sites, respectively. The pharmacological profile of [I-125]VIP and [I-125]PACAP-27 binding to membranes supported the coexistence with VIP receptors of specific receptors for PACAP with a mol wt equal to 67.7K. When [I-125]]PACAP-27 was used, the order of potency of various related peptides for competition of tracer binding was PACAP-27 greater than PACAP-38 greater than VIP. Both PACAP-27 and VIP stimulated adenylate cyclase activity with similar efficacy, although PACAP-27 showed a potency (half-maximal efficient concentration or EC(50) = 0.5 nmol/L) greater than that of VIP (EC(50) = 4.1 nmol/L). When the two peptides were present simultaneously in the incubation medium, no additive effect on the stimulation of adenylate cyclase activity was observed, which suggests a unique receptor coupled to this enzyme.