Identification and functional properties of the pituitary adenylate cyclase activating peptide (PAC(1)) receptor in human benign hyperplastic prostate

Pituitary adenylate cyclase activating peptide (PACAP) is a navel neuropept ide with regulatory and trophic functions that is related to vasoactive int estinal peptide (VIP). Here we investigate the expression of specific PACAP receptors (PAC(1)) and common VIP/PACAP receptors (VPAC(1) and VPAC(2)) in the human hyperplastic prostate by immunological methods. The PAC(1) recep tor corresponded to a 60-KDa protein whereas the already known VPAC(1) and VPAC(2) receptors possessed molecular masses of 58 and 68 KDa, respectively . The heterogeneity of VIP/PACAP receptors in this tissue was confirmed by radioligand binding studies using [I-125]PACAP-27 by means of stoichiometri c and pharmacological experiments. At lease. two classes of PACAP binding s ites showing different affinities could be resolved, with Kd values of 0.81 and 51.4 nM, respectively. The order of potency in displacing [I-125]PACAP -27 binding was PACAP-27 approximate to PACAP-38 > VIP. PACAP-27 and VIP st imulated similarly adenylate: cyclase activity, presumably through common V IP/PACAP receptors. The PAC(1) receptor was not coupled to activation of ei ther adenylate cyclase, nitric oxide synthase, or phospholipase C. It appea rs to be a novel subtype of PAC1 receptor because PACAP-27 (but not PACAP-3 8 or VIP) led to increased phosphoinositide synthesis, an interesting featu re because phosphoinositides are involved via receptor mechanisms in the re gulation of cell proliferation. (C) 1999 Elsevier Science Inc.