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

Abstract

The effect of µ-opioid receptor (MOR) agonist, loperamide on prostate relaxation and the role of potassium channel in this action were studied in isolated Wistar rat prostate. 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. 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. 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.