title: Vasoactive intestinal polypeptide receptor VPAC(1) subtype is predominant in rat prostate membranes.
abstract: BACKGROUND
  The 28-amino-acid neuropeptide vasoactive intestinal peptide (VIP) might play an important role in the physiology of the prostate, since it stimulates glandular secretion, inhibits muscle contraction, stimulates proliferation of epithelial cells, and increases the secretion of prostate-specific antigen (PSA). This neuropeptide may act through interaction with two types of high-affinity receptors, named VPAC(1) and VPAC(2) receptors. Recently, selective agonists and antagonists for each receptor subtype were synthesized. We used them to identify the VIP receptor subclass expressed in 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 VPAC(2) agonist (RO 25-1553). The IC(50) values of [(125)I]-VIP binding inhibition 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 EC(50) values of adenylate cyclase stimulation were similar to the IC(50) values for each peptide, and the Ki values for the VPAC(1) antagonist, inhibiting the adenylate cyclase activity stimulated by VIP and the VPAC(1) agonist, were 22 and 35 nM, respectively. Comparison of binding of [(125)I]-VIP and of [(125)I]-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 predominant. Binding studies were compatible with a ratio of 80/20 of VPAC(1)/VPAC(2) receptors, whereas functionally only VPAC(1) receptors were detected.
authors.affiliation: Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Brussels, Belgium. Juarranz@ulb.ac.be
authors.forename: M G
authors.initials: MG
authors.lastname: Juarranz
authors.forename: P
authors.initials: P
authors.lastname: De Neef
authors.forename: P
authors.initials: P
authors.lastname: Robberecht
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D011467:Prostate / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide / Q000819:agonists / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology
chemical_list: C110307:PG 97-269; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C089777:Ro 25-1553; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases