Thromboxane A2 induces contraction of human prostate smooth muscle by Rho kinase- and calmodulin-dependent mechanisms

Thromboxane A2 (TXA2) induces contraction in different smooth muscle types via its receptor (TXA2 receptor). However, any motoric role of TXA2 in prostate smooth muscle tone has not been studied to date. Here, we investigated whether TXA2 induces contraction of human prostate tissue. After ethical approval, prostate tissue was obtained from 47 patients undergoing radical prostatectomy. Effects of the TXA2 analogue U46619 ((5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptonic acid) in isolated human prostate strips were studied in organ bath experiments with or without the Rho kinase inhibitor, Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride), or the calmodulin antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide hydrochloride). Expression of TXA2 synthase and TXA2 receptors were examined by Western blot analysis and immunohistochemistry. Endogenous TXA2 was quantified by enzyme immunoassay. U46619 induced concentration-dependent contractions of human prostate strips, with a maximum contraction at 3 μM. U46619-induced prostate contraction was significantly inhibited by Y27632 (30 μM) and by W7 (100 μM). TXA2 synthase and TXA2 receptors were detected by Western blot analysis. Immunohistochemical stainings showed that expression of TXA2 synthase in prostate tissue was located to glandular cells, while prostate TXA2 receptors were located to smooth muscle and glandular cells. The stable TXA2 metabolite TXB2 was detected by enzyme immunoassay in the prostate. TXA2 induces contraction of isolated human prostate tissue by TXA2 receptor activation. Prostate smooth muscle TXA2 receptors are coupled to Rho kinase and Ca2+-dependent mechanisms. The distribution of TXA2 synthase and TXA2 receptors in the human prostate suggests TXA2-mediated paracrine epithelial–stromal interactions.