AN INVESTIGATION OF TACHYKININ NK2 RECEPTOR SUBTYPES IN THE RAT

The heterogeneity of tachykinin NK2 receptor subtypes was examined in five tissues from the rat, using binding and functional techniques. In itial experiments with the selective radioligand [I-125[Lys(5),Tyr(I-2 )(7),MeLeu(9),Nle(10)]neuroki A-(4-10) showed no specific binding to r at spinal cord membranes or sections. However, this radioligand exhibi ted high specific binding (80-95% of total) in membranes from the rat fundus, colon, bladder and vas deferens. Dissociation constants (K-D) were lower in bladder and colon (0.4 nM) than in fundus (1.9 nM) or va s deferens (1.4 nM). Neurokinin A, neuropeptide gamma, [Lys(5),MeLeu(9 ),Nle(10)]NK(4-10), SR 48968 piperidino)2-(3,4-dichlorophenyl)butyl]be nzamine], GR 94800 [PhCO-Ala-Ala-DTrp-Phe-DPro-Pro-Nle-NH2] and MEN 10 627 [cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2 beta-5 beta)] displayed hig h affinity (pIC(50) 8.4-9.5) as competitors, with no significant diffe rence in potency between these four tissues. [Lys(5),MeLeu(9),Nle(10)] neurokinin A-(4-10) contracted the isolated fundus (EC50 117 nM) and b ladder (EC50 10 nM) and these responses were similarly inhibited by th e tachykinin NK2 receptor antagonists, SR 48968 and MEN 10627 (pA(2) v alues 7.6-8.2). In spite of differences in K-D seen in some tissues, t hese results do not provide compelling evidence for tachykinin NK2 rec eptor heterogeneity in smooth muscle-containing tissues in the rat. Th e absence of detectable binding in rat spinal cord may be due to very low expression of tachykinin NK2 receptors, or to existence of a diffe rent receptor subtype. (C) 1998 Elsevier Science B.V. All rights reser ved.