Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum
- PMID: 16025145
- PMCID: PMC1576267
- DOI: 10.1038/sj.bjp.0706317
Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum
Abstract
The study was performed to clarify if apomorphine at the level of the rat corpus cavernosum can produce erectile responses or interfere with nerve-induced penile erection. Apomorphine (10(-9)-10(-4) M) exhibited a 10-fold higher potency to relax phenylephrine (Phe)- than endothelin-1 (ET-1)-induced contractions. Relaxant effects of apomorphine in Phe-activated corpus cavernosum did not change tissue levels of cyclic nucleotides, and were unaffected by inhibition of the synthesis of nitric oxide, or by inhibition of the soluble guanylate cyclase. Relaxations by apomorphine of ET-1-contracted rat corpus cavernosum were not influenced by alpha2-adrenoceptor blockade (yohimbine, 10(-7) M), or by the dopamine D1-like receptor antagonist SCH 23390 (10(-6) M). Clozapine (10(-6) M), a proposed dopamine D2-like receptor antagonist, partly reduced apomorphine-induced relaxations, and significantly altered the -log IC50 value for apomorphine. Nerve-induced contractions of the rat corpus cavernosum were attenuated by apomorphine in a concentration-dependent and biphasic manner. Yohimbine (10(-7) M) abolished the biphasic concentration-response pattern. SCH 23390 (10(-6) M) attenuated the inhibitory effects of apomorphine on contractions, and significantly altered the -log IC50 value for the compound. In anesthetized rats (50 mg kg(-1) pentobarbital sodium, 10 mg kg(-1) ketamine), intracavernous apomorphine (100, 300, or 1000 nmol) did not have effects on basal cavernous pressure under resting conditions, and did not affect filling or emptying rates, or peak pressures of the rat corpus cavernosum during submaximal activation of the cavernous nerve. In awake rats, apomorphine produced a maximal number of erections at 300 nmol kg(-1). In the rat isolated corpus cavernosum, pre- and postjunctional effects of apomorphine appear to involve dopamine D1- and D2-like receptors, as well as alpha-adrenoceptors. At relevant systemic doses of apomorphine, peripheral effects of the compound are unlikely to contribute to its proerectile effects in rats.
Figures






Similar articles
-
Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.J Urol. 2002 May;167(5):2276-81. J Urol. 2002. PMID: 11956492
-
Enhancement of apomorphine-induced penile erection in the rat by a selective alpha(1D)-adrenoceptor antagonist.Br J Pharmacol. 2002 Jul;136(5):701-8. doi: 10.1038/sj.bjp.0704773. Br J Pharmacol. 2002. PMID: 12086979 Free PMC article.
-
Peripheral relaxant activity of apomorphine and of a D1 selective receptor agonist on human corpus cavernosum strips.Int J Impot Res. 2005 Mar-Apr;17(2):127-33. doi: 10.1038/sj.ijir.3901293. Int J Impot Res. 2005. PMID: 15549138
-
Nitric oxide as a mediator of cocaine-induced penile erection in the rat.Br J Pharmacol. 1996 May;118(1):155-61. doi: 10.1111/j.1476-5381.1996.tb15379.x. Br J Pharmacol. 1996. PMID: 8733589 Free PMC article.
-
Dopaminergic neurotransmission at the paraventricular nucleus of hypothalamus in central regulation of penile erection in the rat.J Urol. 1999 Jul;162(1):237-42. doi: 10.1097/00005392-199907000-00074. J Urol. 1999. PMID: 10379793
Cited by
-
Molecular and functional characterization of Kv 7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats.Br J Pharmacol. 2016 May;173(9):1478-90. doi: 10.1111/bph.13444. Epub 2016 Feb 26. Br J Pharmacol. 2016. PMID: 26802314 Free PMC article.
-
Relaxant effect and possible mechanism of 17-nor-subincanadine E in rabbit corpora cavernosa.Asian J Androl. 2011 Sep;13(5):747-53. doi: 10.1038/aja.2011.41. Epub 2011 Jul 18. Asian J Androl. 2011. PMID: 21765439 Free PMC article.
-
NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats.Br J Pharmacol. 2009 Nov;158(6):1465-76. doi: 10.1111/j.1476-5381.2009.00404.x. Epub 2009 Oct 20. Br J Pharmacol. 2009. PMID: 19845682 Free PMC article.
-
Hypercaloric Diet Establishes Erectile Dysfunction in Rat: Mechanisms Underlying the Endothelial Damage.Front Physiol. 2017 Oct 4;8:760. doi: 10.3389/fphys.2017.00760. eCollection 2017. Front Physiol. 2017. PMID: 29085300 Free PMC article.
-
Constitutive LH receptor activity impairs NO-mediated penile smooth muscle relaxation.Reproduction. 2021 Jan;161(1):31-41. doi: 10.1530/REP-20-0447. Reproduction. 2021. PMID: 33112284 Free PMC article.
References
-
- ABARCA B., BALLESTEROS R., BIELSA P., MORAGUES J., D'OCON P., GARCIA-ZARAGOZÀ E., NOGUERA M.A. Opposite vascular activity of (R)-apomorphine and its oxidised derivatives. Endothelium-dependent vasoconstriction induced by the auto-oxidation metabolite. Eur. J. Med. Chem. 2003;38:501–511. - PubMed
-
- AMENTA F., BARILI P., BRONZETTI E., FELICI L., MIGNINI F., RICCI A. Localization of dopamine receptor subtypes in systemic arteries. Clin. Exp. Hypertens. 2000;22:277–288. - PubMed
-
- ANDERSSON K.-E. Pharmacology of penile erection. Pharmacol. Rev. 2001;53:417–450. - PubMed
-
- ANWAR N., MASON D.F. Actions of dopamine and apomorphine on the vasoconstrictor responses of perfused mesenteric arteries of mouse, rat and rabbit. J. Pharm. Pharmacol. 1981;33:150–154. - PubMed
-
- BRADFORD M.M. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976;72:248–254. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous