Activation of central melanocortin receptors by MT-II increases cavernosal pressure in rabbits by the neuronal release of NO.

1. Melanotan-II had been reported to cause penile erections in men with erectile dysfunction. In the present study, we investigated the mechanisms by which systemic administration of MT-II increases intracavernosal pressure in anaesthetized rabbits. 2. MT-II (10 microM) had no effect on electrical field stimulation-evoked relaxations of rabbit corpus cavernosal strips in vitro. 3. Intravenous injection of MT-II (66 and 133 microg kg(-1) elicited dose-related increases in cavernosal pressure. SHU 9119 (3 microg kg(-1), i.v.), a non-selective antagonist of MC(3) and MC(4) receptors did not significantly affect either cavernosal pressure or systemic blood pressure but abolished the MT-II-induced increases in cavernosal pressure. SHU 9119 also inhibited the depressor response produced by MT-II. 4. Intracavernosal injection 100 microl of the cocktail containing phentolamine mesylate (1 mg ml(-1)), papaverine (20 mg ml(-1)) and PGE1 (20 microg ml(-1)) increased the cavernosal pressure by about 4 fold. 5. The role of NO-cyclic GMP dependent pathway to MT-II-induced increases in cavernosal pressure was investigated by bilateral transection of the pudendal nerves and by inhibition of NO synthase with L-NAME (20 mg kg(-1), i.v. over 30 min). Ablation of the pudendal nerves or pretreatment with L-NAME abolished the MT-II-induced increases in intracavernosal pressure in anaesthetized rabbits. 6. The data suggest that activation of central melanocortin receptors by MT-II increases cavernosal pressure by the neuronal release of NO.