RECEPTORS FOR PITUITARY ADENYLATE-CYCLASE ACTIVATING PEPTIDES IN HUMAN PITUITARY-ADENOMAS

The presence of pituitary adenylate cyclase activating polypeptide (PA CAP) receptors coupled to adenylate cyclase was investigated in four t ypes of human pituitary adenomas: three null adenomas and five gonadot ropin-, three ACTH-, four GH-, and four PRL-producing adenomas. In all samples, except in prolactinomas, PACAP(1-27) and PACAP(1-38) stimula ted adenylate cyclase activity equally well and potently (K-act around 3 nmol). Vasoactive intestinal polypeptide (VIP) was systematically 1 00- to 300-fold less potent than both PACAPs. In prolactinomas, PACAP( 1-27), PACAP(1-38), and VIP were inactive despite a response of the en zyme to guanosine 5'-triphosphate, Gpp(NH)p, forskolin, and fluoride. [I-125-AcHis(1)]PACAP(1-27) binding was detected in all samples except in prolactinomas. In addition, a detailed analysis of receptors was f easible in all five gonadotropin- and in two ACTH-producing adenomas, confirming the existence of selective PACAP receptors that recognized PACAP(1-27) and PACAP(1-38) with similar high affinity (IC50 0.8-1.5 n mol) and VIP with a low affinity (Ic(50) 100 nmol/L).