Rm. Solano et al., CHARACTERIZATION OF VASOACTIVE INTESTINAL PEPTIDE PITUITARY ADENYLATECYCLASE-ACTIVATING PEPTIDE RECEPTORS IN HUMAN BENIGN HYPERPLASTIC PROSTATE/, Endocrinology, 137(7), 1996, pp. 2815-2822
Vasoactive intestinal peptide (VIP) is an important member of the grou
p of neuropeptides that appears to be involved in the regulation of pr
ostatic growth and function. Here we studied VIP receptors in membrane
s from human benign hyperplastic prostate. Accordingly to observations
in rat prostatic membranes, [I-125]VIP binding to human prostatic mem
branes suggested two classes of binding sites with high (K-d = 0.22 nM
) and low (K-d = 37.7 nM) affinities. VIP bound in human and rat membr
ane preparations to a common VIP/pituitary adenylate cyclase-activatin
g peptide (PACAP) receptor, as VIP, PACAP-27, and PACAP-38 were equipo
tent for competition of [I-125]VIP binding. A PACAP-preferring recepto
r appears to be expressed in human prostate, since [I-125]PACAP bindin
g was displaced with more potency by PACAP than by VIP, and a messenge
r RNA corresponding to type I PACAP receptor was found. Cross-linking
experiments suggested a VIP receptor of about 71 kDa in human and 52 k
Da in rat prostates. The binding of [I-125]VIP to membranes and the la
beling of the bands observed after electrophoresis were competitively
inhibited by GTP, suggesting the coupling of VIP receptors to a G prot
ein. Moreover, after solubilization and cross-linking, we observed a 1
20-kDa band that corresponded to the VIP receptor-alpha(s) association
. VIP stimulated adenylyl cyclase activity in a dose-dependent manner,
but the potency and/or the efficacy of VIP were lower in all human pr
eparations studied than in rat prostatic membranes. In conclusion, thi
s study clearly demonstrates the expression of VIP/PACAP common recept
ors associated with alpha(s) protein in human prostate and suggests th
at these neuropeptides could play an important and complex role in the
physiology and pathophysiology of this human gland.