Stimulation of epithelial CB1 receptors inhibits contractions of the rat prostate gland

Background and purpose: This study investigated whether stimulation of cannabinoid receptors influences smooth muscle contractility in the rat prostate gland. Experimental approach: Immunohistochemistry was used to characterize and localize cannabinoid receptors in the rat prostate gland. Isolated organ bath experiments were carried out to investigate the effects of cannabinoids on prostate contractility. Key results: Immunohistochemical studies of the rat prostate yielded positive immunoreactivity for the CB1 receptor, but not the CB2 receptor. Double labelling revealed that CB1 receptors were not colocalized with alpha-actin in the smooth muscle layer but were primarily expressed within the epithelial lining of the prostatic acini. The cannabinoid receptor agonist WIN 55,212-2 (10 nM - 10 mu M) inhibited contractile responses to electrical-field stimulation (10 Hz, 0.5 ms, 60 V for 2 s per minute) in a concentration-dependent manner. The CB1 selective antagonists, SR141716 (1 mu M) and LY 320135 (1 mu M), reversed the WIN 55,212-2-mediated inhibition but the CB2 selective antagonist, SR144528 (1 mu M), did not. Furthermore, the cyclooxygenase inhibitor indomethacin (0.1 mu M) caused significant reversal of the WIN 55,212-2 mediated inhibition of contractile responses, whereas the nitric oxide synthase inhibitor N-omega-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 mM) did not. Prostaglandin E-2 (10 nM - 10 mM), produced a similar concentration-dependent inhibition to WIN 55,212-2. Conclusions and implications: WIN 55,212-2, an agonist at cannabinoid receptors, causes inhibition of smooth muscle contraction in the rat prostate by activating epithelial CB1 receptors. This inhibition is mediated via the cyclooxygenase pathway.