Receptors for pituitary adenylate cyclase activating peptides in human pituitary adenomas.
The presence of pituitary adenylate cyclase activating polypeptide (PACAP) receptors coupled to adenylate cyclase was investigated in four types of human pituitary adenomas: three null adenomas and five gonadotropin-, three ACTH-, four GH-, and four PRL-producing adenomas. In all samples, except in prolactinomas, PACAP(1-27) and PACAP(1-38) stimulated adenylate cyclase activity equally well and potently (K(act) around 3 nmol). Vasoactive intestinal polypeptide (VIP) was systematically 100- 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 enzyme to guanosine 5'-triphosphate, Gpp(NH)p, forskolin, and fluoride. [125I-AcHis1]PACAP(1-27) binding was detected in all samples except in prolactinomas. In addition, a detailed analysis of receptors was feasible 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 nmol) and VIP with a low affinity (IC50 100 nmol/L).
Robberecht
P
P
Department of Biochemistry and Nutrition, Erasme Hospital, Medical School, Université Libre de Bruxelles, Belgium.
Vertongen
P
P
Velkeniers
B
B
de Neef
P
P
Vergani
P
P
Raftopoulos
C
C
Brotchi
J
J
Hooghe-Peters
E L
EL
Christophe
J
J
D000236:Adenoma / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D009479:Neuropeptides / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010911:Pituitary Neoplasms / Q000378:metabolism*; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases