MODULATION OF THE CONTRACTION OF RAT VAS DEFERENS BY TRPM8 ACTIVATION

The influence of menthol (100µM) on the contractile responses evoked by high potassium (60 mM), noradrenaline and carbachol were examined in the smooth muscle preparations from prostatic and epididimal portions of the rat vas deferens. All agonist-induced contractions were greatly increased in the prostatic and suppressed in the epididimal portions of the vas deferens from orchidectomized rats as compared with those from normal animals. Menthol did not change the basal tonus of isolated strips of the vas deferens, but decreased the magnitudes of agonist- and KCl-induced contractions in both groups of animals. The same effects were observed with more specific agonist of TRPM8 channel, icilin (10 µM) suggesting TRPM8 involvement. The inhibitory action of menthol and icilin was not dependent on the presence of the epithelium. Real-time RT-PCR showed two-fold higher TRPM8 expression in the smooth muscle tissue (without epithelium) from epididimal vs. prostatic parts of the vas deferens of control rats. Following orchidectomization TRPM8 expression increased 1.5-fold in epididimal portion and almost 3-fold in the prostatic portion. The enhancement of TRPM8 expression was paralleled by the increase in androgen receptor expression. We conclude that TRPM8 activation modulates contractility of the vas deferens in androgen-dependent manner, which may play role in the control of its physiological contractile function, however, the mechanism of such modulation needs further investigation. Supported in part by INTAS 05-1000008-8223 grant.