Vasoactive intestinal polypeptide receptor VPAC(1) subtype is predominant in rat prostate membranes

BACKGROUND. The 28-amino-acid neuropeptide vasoactive intestinal peptide (V IP) might play an important role in the physiology of the prostate, since i t stimulates glandular secretion, inhibits muscle contraction, stimulates p roliferation of epithelial cells, and increases the secretion of prostate-s pecific antigen (PSA). This neuropeptide may act through interaction with t wo types of high-affinity receptors, named VPAC(1) and VPAC(2) receptors. R ecently, selective agonists and antagonists for each receptor subtype were synthesized. We used them to identify the VIP receptor subclass expressed i n rat prostatic tissue. METHODS. We tested the capacity of selective labeled and unlabeled agonists and antagonists of VPAC(1) and VPAC(2) receptors to bind to rat prostatic membranes and to stimulate or prevent the stimulation of adenylate cyclase activity. RESULTS. The following selective peptides were used: VPAC(1) agonist ([K-15 , R-16, L-27] VIP (1-7)/GRF (8-27)); VPAC(1) antagonist (PG 97-269); and VP AC(2) agonist (RO 25-1553). The IC50 values of [I-125]-VIP binding inhibiti on for the different peptides in rat prostatic membranes were: VIP (1.7 nM) < VPAC(1) agonist (20 nM) < VPAC(1) antagonist (40 nM) < VPAC(2) agonist ( 329 nM). The EC50 values of adenylate cyclase stimulation were similar to t he IC50 values for each peptide, and the Ki values for the VPAC(1) antagoni st, inhibiting the adenylate cyclase activity stimulated by VIP and the VPA C(1) agonist, were 22 and 35 nM, respectively. Comparison of binding of [I- 125]-VIP and of [I-125]-RO 25-1553 indicates the presence of 80% of VPAC(1) and 20% VPAC(2) receptors. CONCLUSIONS. In rat prostate membranes, VPAC(1) receptors are largely predo minant. Binding studies were compatible with a ratio of 80/20 of VPAC(1)/VP AC(2) receptors, whereas functionally only VPAC(1) receptors were detected. Prostate 41:1-6, 1999. (C) 1999 Wiley-Liss, Inc.