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

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Abstract
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. MT‐II (10 μM) had no effect on electrical field stimulation‐evoked relaxations of rabbit corpus cavernosal strips in vitro. Intravenous injection of MT‐II (66 and 133 μg kg−1 elicited dose‐related increases in cavernosal pressure. SHU 9119 (3 μg kg−1, i.v.), a non‐selective antagonist of MC3 and MC4 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. Intracavernosal injection 100 μl of the cocktail containing phentolamine mesylate (1 mg ml−1), papaverine (20 mg ml−1) and PGE1 (20 μg ml−1) increased the cavernosal pressure by about 4 fold. 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. The data suggest that activation of central melanocortin receptors by MT‐II increases cavernosal pressure by the neuronal release of NO. British Journal of Pharmacology (2001) 134, 1705–1710; doi:10.1038/sj.bjp.0704437

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