An immunohistochemical and pharmacological study of tachykinins in the ratand guinea-pig prostate glands

This study investigated the presence and effects of tachykinin peptides wit hin the rat and guinea-pig prostate glands. Immunohistochemical studies dem onstrated the presence of substance P and neurokinin A immunoreactive nerve fibres, sparsely distributed throughout the prostatic fibromuscular stroma in both species. In organ bath experiments, nerve terminals within rat and guinea-pig prostatic tissues were electrically field stimulated (60 V, 0.5 ms, 10 Hz, 20 pulses every 50 s). In rat preparations, the exogenous appli cation of substance P, neurokinin A and the tachykinin NK3 receptor agonist senktide (1 nM-1 mu M:) had no effect on contractile responses. In contras t, substance P and neurokinin A (1 nM-3 mu M) concentration-dependently enh anced electrically-evoked contractile responses in the guinea-pig prostate. Senktide was without effect. The potentiation of electrical field stimulat ion-induced contractions by substance P and neurokinin A in the guinea-pig prostate was competitively antagonized by ((S)1-{2-[3-(3,4-dichlorophenyl)- 1-(3-isopropoxyphenylacetyl) piperidin-3-yl]ethyl}-4-phenyl-1-azonia-bicycl o[2.2.2]octane, chloride) (SR 140333) at 10 nM, a tachykinin NK1 receptor a ntagonist. The tachykinin NK2 receptor antagonist (S)-N-methyl-N[4-(4-acety lamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide (SR 48968) was without effect at 10 nM, suggesting that neuromodulation of electrical ly-evoked contractions in the guinea-pig prostate occurs through activation of a tachykinin NK1 receptor subtype. (C) 1999 Elsevier Science B.V. All r ights reserved.