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

Abstract

This study investigated the presence and effects of tachykinin peptides within the rat and guinea-pig prostate glands. Immunohistochemical studies demonstrated 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 application of substance P, neurokinin A and the tachykinin NK 3 receptor agonist senktide (1 nM–1 μM) had no effect on contractile responses. In contrast, substance P and neurokinin A (1 nM–3 μM) concentration-dependently enhanced electrically-evoked contractile responses in the guinea-pig prostate. Senktide was without effect. The potentiation of electrical field stimulation-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-bicyclo[2.2.2]octane, chloride) (SR 140333) at 10 nM, a tachykinin NK 1 receptor antagonist. The tachykinin NK 2 receptor antagonist ( S)- N-methyl- N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide (SR 48968) was without effect at 10 nM, suggesting that neuromodulation of electrically-evoked contractions in the guinea-pig prostate occurs through activation of a tachykinin NK 1 receptor subtype.