[Urothelium-dependent modulation of urinary bladder smooth muscle contractions by menthol].

TRPM8 cold receptor/channel is considered amongst the variety of receptors that support and modulate sensory function of urothelium, although the information regarding this is still quite contradictory. Here we have studied the effects of nonspecific TRPM8 activator menthol on the contractions of the smooth muscle strips of the rat bladder with intact and removed urothelium, and assessed the expression in them of TRPM8 mRNA using semi-quantitative RT-PCR. Menthol (100 microM) decreased the basal tone and the amplitude of spontaneous contractions only in the strips with intact urothelium. Irrespective of the presence of urothelium it similarly inhibited (by approximately 45 %) the contractions evoked by high-potassium depolarization. Contractions induced by muscarinic agonist carbachol (1 microM) were inhibited by menthol much stronger (by approximately 63%) if the urothelium was present than without it (by approximately 12%). Expression of TRPM8 mRNA in urothelium was not detected, whilst in detrusor smooth muscle it was found very low. We conclude that modulation of contractile responses by menthol is most likely explained by its blocking action on voltage-gated calcium channels ofdetrusor smooth muscle cells (SMC) and by menthol-stimulated release from urothelium of some factor(s) with relaxant effects on SMCs. Stimulation of the secretion of these factors from urothelial cells most likely involves menthol-induced, TRPM8-independent mobilization of calcium.