Control of penile erection by the melanocortinergic system: Experimental evidences and therapeutic perspectives

Journal of Andrology

Volumn 25, Issue 5, 2004, Pages 683-691

  Giuliano, François ^a,b,c  

^a CNRS   (France)

^b UPRES 4122   (France)

^c BICÊTRE HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

HORMONE RECEPTOR STIMULATING AGENT; MELANOCORTIN; MELANOCORTIN RECEPTOR; MELANOCORTIN RECEPTOR AGONIST; MT II; N ACETYLNORLEUCYLASPARTYLHISTIDYL DEXTRO PHENYLALANYLARGINYLTRYPTOPHYLLYSINE 2,7 CYCLIC AMIDE; UNCLASSIFIED DRUG;

CENTRAL NERVOUS SYSTEM; CLINICAL TRIAL; CONTROL SYSTEM; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; ERECTILE DYSFUNCTION; HUMAN; MUSCLE CONTRACTION; NAUSEA; NEUROTRANSMITTER RELEASE; PENIS ERECTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECEPTOR BINDING; REVIEW; SIDE EFFECT; SKIN PIGMENTATION; SMOOTH MUSCLE RELAXATION; SYMPATHETIC BLOCKING; VOMITING;

EID: 4143081589     PISSN: 01963635     EISSN: None     Source Type: Journal    
DOI: 10.1002/j.1939-4640.2004.tb02842.x     Document Type: Review

References (57)

1. Abdel-Malek ZA. Melanocortin receptors: their functions and regulation by physiological agonists and antagonists. Cell Mol Life Sci. 2001; 58:434-441.
2. Adan RA, Gispen WH. Melanocortins and the brain: from effects via receptors to drug targets. Eur J Pharmacol. 2000;405:13-24.
3. Andersson KE. Pharmacology of penile erection. Pharmacol Rev. 2001; 53:417-450.
4. Argiolas A, Melis MR, Mauri A, Gessa GL. Paraventricular nucleus lesion prevents yawning and penile erection induced by apomorphine and oxytocin but not by ACTH in rats. Brain Res. 1987a;421:349-352.
5. Argiolas A, Melis MR, Murgia S, Schioth HB. ACTH- and alpha-MSH-induced grooming, stretching, yawning and penile erection in male rats: site of action in the brain and role of melanocortin receptors. Brain Res Bull. 2000;51:425-431.
6. Argiolas A, Melis MR, Stancampiano R, Gessa GL. Role of calcium in the expression of ACTH-induced stretching, yawning and penile erection. Brain Res Bull. 1990;24:853-856.
7. Argiolas A, Melis MR, Vargiu L, Gessa GL. d(CH2)5Tyr(Me)-[Orn8]vasotocin, a potent oxytocin antagonist, antagonizes penile erection and yawning induced by oxytocin and apomorphine, but not by ACTH-(1-24). Eur J Pharmacol. 1987b;134:221-224.
8. Avis NE. Sexual function and aging in men and women: community and population-based studies. J Gend Specif Med. 2000;3:37-41.
9. Bertolini A, Gessa GL. Behavioral effects of ACTH and MSH peptides. J Endocrinol Invest. 1981;4:241-251.
10. Bertolini A, Gessa GL, Ferrari C. Penile erection and ejaculation: a central effect of ACTH-like peptides in mammals. In: Sandler M, Gessa GL, eds. Sexual Behavior: Pharmacology and Biochemistry. New York: Raven Press; 2001:247-257.
11. Dines KC, Gahman TC, Girten BE, et al, inventors. Melanocortin receptor-3 ligands to treat sexual dysfunction. US patent 6 534 50. March 2003.
12. Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58:1777-1784.
13. Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 1997;385:165-168.
14. Ferrari W, Gessa GL, Vargiu L. Behavioural effects induced by intracisternally injected ACTH and MSH. Ann N Y Acad Sci. 1963;104: 330-345.
15. Giuliano F. Phosphodiesterase type 5 inhibition in erectile dysfunction: an overview. Eur Heart J. 2002;4:H7-H12.
16. Giuliano F, Allard J. Apomorphine SL (Uprima): preclinical and clinical experiences learned from the first central nervous system-acting ED drug. Int J Impot Res. 2002;14(suppl 1):S53-S56.
17. Giuliano F, Bernabé J, Brown K, Droupy S, Benoit G, Rampin O. Erectile response to hypothalamic stimulation in rats: role of peripheral nerves. Am J Physiol. 1997;273:R1990-R1997.
18. Giuliano F, Rampin O. Central neural regulation of penile erection. Neurosci Biobehav Rev. 2000;24:517-533.
19. Giuliano FA, Rampin O, Benoit G, Jardin A. Neural control of penile erection. Urol Clin North Am. 1995;22:747-766.
20. Hadley ME, Haskell-Luevano C. The proopiomelanocortin system. Ann N Y Acad Sci. 1999;885:1-21.
21. Hedlund H, Andersson KE. Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery. J Urol. 1985;134:1245-1250.
22. Kask A, Mutulis F, Muceniece R, Pahkla R, Mutule I, Wikberg JE, Rago L, Schioth HB. Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): evaluation in vitro and in vivo. Endocrinology. 1998;139:5006-5014.
23. Kishi T, Aschkenasi CJ, Lee CE, Mountjoy KG, Saper CB, Elmquist JK. Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J Comp Neurol. 2003;457:213-235.
24. Lindblom J, Schioth HB, Larsson A, Wikberg JE, Bergstrom L. Autoradiographic discrimination of melanocortin receptors indicates that the MC3 subtype dominates in the medial rat brain. Brain Res. 1998; 810:161-171.
25. Lu D, Willard D, Patel IR, et al. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature. 1994;371:799-802.
26. Martin WJ, McGowan E, Cashen DE, et al. Activation of melanocortin MC(4) receptors increases erectile activity in rats ex copula. Eur J Pharmacol. 2002;454:71-79.
27. McKenna K. The brain is the master organ in sexual function: central nervous system control of male and female sexual function. Int J Impot Res. 1999;(suppl 1):S48-S55.
28. Mizusawa H, Hedlund P, Andersson KE. alpha-Melanocyte stimulating hormone and oxytocin induced penile erections, and intracavernous pressure increases in the rat. J Urol. 2002;167:757-760.
29. Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003;994:96-102.
30. Moreland RB, Nakane M, Hsieh G, Brioni JD. Prospectives for pharmacotherapy of male erectile dysfunction. Curr Opin CPNS Investig Drugs. 2000;2:283-302.
31. Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol. 1994;8:12981308.
32. Mountjoy KG, Wild JM. Melanocortin-4 receptor mRNA expression in the developing autonomic and central nervous systems. Brain Res Dev Brain Res. 1998;107:309-314.
33. Nagahama M, Funasaka Y, Fernandez-Frez ML, Ohashi A, Chakraborty AK, Ueda M, Ichihashi M. Immunoreactivity of alpha-melanocyte-stimulating hormone, adrenocorticotrophic hormone and beta-endorphin in cutaneous malignant melanoma and benign melanocytic naevi. Br J Dermatol. 1998;138:981-985.
34. Poggioli R, Benelli A, Arletti R, Cavazzuti E, Bertolini A. Nitric oxide is involved in the ACTH-induced behavioral syndrome. Peptides. 1995;16:1263-1268.
35. Rampin O, Bernabe J, Giuliano F. Spinal control of penile erection. World J Urol. 1997;15:2-13.
36. Roselli-Rehfuss L, Mountjoy KG, Robbins LS, et al. Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc Natl Acad Sci U S A. 1993;90:8856-8860.
37. Saenz de Tejada I. Molecular mechanisms for the regulation of penile smooth muscle contractility. Int J Impot Res. 2002;14(suppl 1):S6-S10.
38. Schioth HB, Muceniece R, Mutulis F, Bouifrouri AA, Mutule I, Wikberg JE. Further pharmacological characterization of the selective melanocortin 4 receptor antagonist HS014: comparison with SHU9119. Neuropeptides. 1999;33:191-196.
39. Schmidt MH, Schmidt HS. The ischiocavernosus and bulbospongiosus muscles in mammalian penile rigidity. Sleep. 1993;16:171-183.
40. Sebhat IK, Martin WJ, Ye Z, et al. Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium-3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl) -2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist. J Med Chem. 2002;45:4589-4593.
41. Serra G, Collu M, Loddo S, Celasco G, Gessa GL. Hypophysectomy prevents yawning and penile erection but not hypomotility induced by apomorphine. Pharmacol Biochem Behav. 1983;19:917-919.
42. Serra G, Fratta W, Collu M, Gessa GL. Hypophysectomy prevents ACTH-induced yawning and penile erection in rats. Pharmacol Biochem Behav. 1987;26:277-279.
43. Shutter JR, Graham M, Kinsey AC, Scully S, Luthy R, Stark KL. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev. 1997;11: 593-602.
44. Stackl W, Hasun R, Marberger M. Intracavernous injection of prostaglandin El in impotent men. J Urol. 1988;140:66-68.
45. Stengaard-Pedersen K, Larsson LI. Comparative immunocytochemical localization of putative opioid ligands in the central nervous system. Histochemistry. 1981;73:89-114.
46. Tsou K, Khachaturian H, Akil H, Watson SJ. Immunocytochemical localization of pro-opiomelanocortin-derived peptides in the adult rat spinal cord. Brain Res. 1986;378:28-35.
47. van der Kraan M, Adan RA, Entwistle ML, Gispen WH, Burbach JP, Tatro JB. Expression of melanocortin-5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands. Endocrinology. 1998;139:2348-2355.
48. van der Kraan M, Tatro JB, Entwistle ML, Brakkee JH, Burbach JP, Adan RA, Gispen WH. Expression of melanocortin receptors and pro-opiomelanocortin in the rat spinal cord in relation to neurotrophic effects of melanocortins. Brain Res Mol Brain Res. 1999;63:276-286.
49. Van der Ploeg LH, Martin WJ, Howard AD, et al. A role for the melanocortin 4 receptor in sexual function. Proc Natl Acad Sci U S A. 2002; 99:11381-11386.
50. Vemulapalli R, Kurowski S, Salisbury B, Parker E, Davis H. Activation of central melanocortin receptors by MT-II increases cavernosal pressure in rabbits by the neuronal release of NO. Br J Pharmacol. 2001; 134:1705-1710.
51. Vergoni AV, Bertolini A, Mutulis F, Wikberg JE, Schioth HB. Differential influence of a selective melanocortin MC4 receptor antagonist (HS014) on melanocortin-induced behavioral effects in rats. Eur J Pharmacol. 1998;362:95-101.
52. Vergoni AV, Sandrini M, Filaferro M, Bertolini A. Opening of brain potassium-channels inhibits the ACTH-induced behavioral syndrome in the male rat. Neurosci Lett. 1995;188:29-32.
53. Voisey J, Carroll L, van Daal A. Melanocortins and their receptors and antagonists. Curr Drug Targets. 2003;4:586-597.
54. Wessells H, Fuciarelli K, Hansen J, Hadley ME, Hruby VJ, Dorr R, Levine N. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J Urol. 1998;160:389-393.
55. Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N. Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction. Urology. 2000;56:641-646.
56. Wessells H, Hruby VJ, Hackett J, Han G, Balse-Srinivasan P, Vanderah TW. Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 induces penile erection via brain and spinal melanocortin receptors. Neuroscience. 2003; 118:755-762.
57. Wikberg JE, Muceniece R, Mandrika I, Prusis P, Lindblom J, Post C, Skottner A. New aspects on the melanocortins and their receptors. Pharmacol Res. 2000;42:393-420.