NPY RECEPTOR SUBTYPES INVOLVED IN THE CONTRACTION OF THE PROXIMAL COLON OF THE RAT

Experiments were designed to determine the receptor subtype(s) involve d in the contraction of the rat proximal colon to NPY. In this tissue, mRNA of Y-2 and Y-4 NPY receptor subtypes were highly expressed, wher eas Y-5 mRNA levels were very low and Y-1 mRNA levels were intermediat e. NPY analogues induced contractions with the following order of pote ncy: rPP > hPP = PYY - NPY = [Leu(31), Pro(34)]NPY > NPY(2-36) = [D-Tr p(32)]Npy > NPY(13-36). Responses to NPY, PYY and NPY(13-36) were not or partially affected by tetrodotoxin, in contrast to the responses to [Leu(31),Pro(34)]Npy, rPP, hPP and [D-Trp(32)]NPY which were fully bl ocked. Atropine did not inhibit the contractions to NPY, PYY and [Leu( 31),Pro(34)]NPY but significantly affected those to NPY(13-36), [D-Trp (32)]Npy, rPP and hPP. The specific Y-1 receptor antagonist BIBP 3226 was ineffective but JCF 104 and JCF 105 (two compounds with preferenti al affinity toward the hY(5) receptor versus the hY(1) or hY(2) recept or) abolished the contractions provoked by the NPY analogues. These re sults suggest that NPY activates three receptor subtypes, a Y-2 subtyp e possibly by a direct action on the smooth muscle cells, as well as a Y-4 and a Y-5 (or 'Y-5-like') subtype which, respectively, release ac etylcholine and an unknown neurotransmitter. (C) 1998 Elsevier Science B.V. All rights reserved.