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5-HT(2C) receptor activation is a common mechanism on proerectile effects of apomorphine, oxytocin and melanotan-II in rats.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2008 Jul 28; Vol. 589 (1-3), pp. 157-62. Date of Electronic Publication: 2008 May 24. - Publication Year :
- 2008
-
Abstract
- 5-Hydroxytryptamine (5-HT), dopamine, oxytocin and melanocortin pathways are known to be involved in the induction of penile erections in rats. Although a dopamine-oxytocin-5-HT link in the central nervous system has been suggested to be important to the control of penile erections, the 5-HT receptor subtype that mediates dopamine-oxytocin-5-HT action and the relationship between the dopamine-oxytocin-5-HT pathway and melanocortin pathway have not been fully elucidated. In this study, in order to clarify these matters, we examined the effects of a selective 5-HT(2B)/5-HT(2C) receptors antagonist, 1-(1-methylindol-5-yl)-3-(3-pyridyl)urea (SB200646) and a selective 5-HT(2C) receptor antagonist, 6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy) pyridin-3-yl carbamoyl] indoline (SB242084) on penile erections induced by a dopamine receptor agonist, 10, 11-dihydroxyaporphine (apomorphine), oxytocin, or a melanocortin receptor agonist, melanotan-II (MT-II) in rats. SB200646 at 10 mg/kg and SB242084 at 3 mg/kg, these doses which completely antagonize penile erections induced by 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP) and (S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348), significantly inhibited penile erections elicited by apomorphine, oxytocin or MT-II. In addition, in order to clarify further the suggestion that the 5-HT pathway projecting from medulla oblongata to lumbosacral spinal site and lumbosacral 5-HT(2C) receptor are involved in the induction of penile erection, we also examined the proerectile effect of YM348 in spinal and a 5-HT depletor, p-chlorophenyl alanine (pCPA)-treated rats. YM348 induced intracavernous pressure increase in spinal and pCPA-treated rats as well as normal rats. These results suggest that 5-HT(2C) receptor in lumbosacral spinal sites mediates not only dopamine-oxytocin-5-HT action but melanocortin action on penile erections, and that the 5-HT pathway is located downstream from melanocortin pathway as well as the dopamine-oxytocin pathway.
- Subjects :
- Aminopyridines pharmacology
Animals
Dose-Response Relationship, Drug
Indazoles pharmacology
Indoles pharmacology
Lumbosacral Region
Male
Medulla Oblongata metabolism
Neural Pathways drug effects
Neural Pathways metabolism
Piperazines pharmacology
Pressure
Rats
Rats, Wistar
Receptor, Serotonin, 5-HT2B drug effects
Receptor, Serotonin, 5-HT2B metabolism
Receptor, Serotonin, 5-HT2C metabolism
Serotonin Antagonists pharmacology
Serotonin Receptor Agonists pharmacology
Spinal Cord metabolism
Urea analogs & derivatives
Urea pharmacology
alpha-MSH pharmacology
Apomorphine pharmacology
Dopamine Agonists pharmacology
Medulla Oblongata drug effects
Oxytocin pharmacology
Penile Erection drug effects
Penis innervation
Peptides, Cyclic pharmacology
Receptor, Serotonin, 5-HT2C drug effects
Spinal Cord drug effects
alpha-MSH analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 589
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18582863
- Full Text :
- https://doi.org/10.1016/j.ejphar.2008.05.022