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

Abstract

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.

• Authors: R Vemulapalli, S Kurowski, B Salisbury, E Parker, H Davis
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 134 Issue 8 Pg. 1705-10 (Dec 2001) ISSN: 0007-1188 [Print] England
• PMID: 11739247 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Peptides, Cyclic
• Receptors, Corticotropin
• Receptors, Melanocortin
• melanotan-II
• SHU 9119
• Nitric Oxide
• alpha-MSH
• Melanocyte-Stimulating Hormones
• Papaverine
• Nitric Oxide Synthase
• Alprostadil
• Cyclic GMP
• NG-Nitroarginine Methyl Ester
• Phentolamine

Topics

• Alprostadil (pharmacology)
• Anesthesia
• Animals
• Blood Pressure (drug effects)
• Culture Techniques
• Cyclic GMP (metabolism)
• Dose-Response Relationship, Drug
• Electric Stimulation
• Enzyme Inhibitors (pharmacology)
• Injections, Intravenous
• Isometric Contraction (drug effects)
• Male
• Melanocyte-Stimulating Hormones (pharmacology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Neurons (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Papaverine (pharmacology)
• Penis (blood supply, drug effects, innervation, physiology)
• Peptides, Cyclic (administration & dosage, pharmacology)
• Phentolamine (pharmacology)
• Rabbits
• Receptors, Corticotropin (metabolism)
• Receptors, Melanocortin
• alpha-MSH (administration & dosage, analogs & derivatives, pharmacology)