NK2 receptors mediate tachykinin-induced contractions of rat uterus duringthe oestrous cycle

We examined tachykinin-induced contractions of uteri from rats during the o estrous cycle. The potencies of substance P, neurokinin A, neurokinin B and the tachykinin NK2 receptor-selective agonist, [Lys(5), MeLeu(9), Nle(10)] neurokinin A-(4-10), and of the non-peptide tachykinin NK1, NK2 and NK3 re ceptor antagonists (S)1-{2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylace tyl)piperidin-3-yl]ethyl}-4-phenyl-1-azonia-bicyclo[2.2.2]octane (SR 140333 ), (S)-N-methyl-N [4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophen yl)butyl]benzamide (SR 48968) and (S)-( N)-(1-(3-(1-benzoyl-3-(3,4-dichloro phenyl)piperidin-3-yl)propyl) N-methylacetamide (SR 142801), were examined. The relative agonist potencies, i.e., [Lys(5), MeLeu(9), Nle(10)] neurokin in A-(4-10) greater than or equal to neurokinin A > neurokinin B greater th an or equal to substance P were similar in preparations from rats in dioest rus/metoestrus and those in proestrus/oestrus. Apparent pK(B) values for SR 48968 versus neurokinin A and [Lys(5), MeLeu(9), Nle(10)] neurokinin A-(4- 10), were 9.9 and 9.2, respectively, indicating activation of an NK2 recept or. SR 140333 (10 nM) produced only a small rightward shift of the log conc entration-response curve to substance P. SR 48968 (3 nM), but not SR 142801 (100-300 nM) reduced the effect of neurokinin B. These data indicate that in the rat tachykinin-induced contract-ions of the uteri during the oestrou s cycle are mediated primarily by tachykinin NK2 receptors, and that fluctu ations in ovarian hormonal levels during the oestrous cycle have little inf luence on the uterine response to tachykinins. (C) 1999 Elsevier Science B. V. All rights reserved.