Loperamide-induced rat prostate relaxation through activation of peripheral μ-opioid receptors

Aims: The effect of m-opioid receptor (MOR) agonist, loperamide on prostate relaxation and the role of potassium channel in this action were studied in isolated Wistar rat prostate. Methods: Tissue strips from rat prostate ventral lobe were hung in organ bath containing: group 1: standard Tyrode's solution (TS); group 2: TS with 1 μM naloxone; group 3: TS with 0.1 μM naloxonazine; and group 4: TS with 0.01-1 μM glybenclamide. The strips were pre-contracted with either 50 mM KCl or 1 μM phenylephrine. Dose-response study on the prostate strip was performed by cumulative administration of loperamide 0.1-10 μM into the organ bath. Western blot study was performed to detect the presence of MOR protein and adenosine triphosphate (ATP)-sensitive potassium channel (K_ATP) subunit Kir6.2 protein expressions in the prostate tissue. Results: Loperamide induced relaxation of the pre-contracted prostate strips in a dose-dependent fashion. Pre-treatment with 1 μM naloxone significantly inhibited the relaxation, thus suggesting activation of MOR in the loperamide effect. Pre-treatment with 0.1 μM naloxonazine inhibited relaxation only in the phenylephrine-contracted strips. The K_ATP channel blocker glybenclamide significantly inhibited the loperamide-induced relaxation, indicating involvement of K_ATP channels in mediating the prostate relaxation. Western blots showed the expression of MOR and Kir6.2 protein in the rat prostate. Conclusions: MOR and Kir6.2 are expressed in the rat prostate and loperamide induces rat prostate relaxation through activation of peripheral MOR. K_ATP channels are involved in mediating the effect of loperamide on the relaxation of prostate.