Abstract
We described earlier that an alkaloid-rich fraction (F3–5) from Aspidosperma ulei (Markgr) induces penile erection-like behavioral responses in mice. This study verified a possible relaxant effect of this fraction on isolated rabbit corpus cavernosum (RbCC) strips precontracted by phenylephrine (1 μM) or K+ 60 mM. F3–5 (1–300 μg ml−1) relaxed the RbCC strips in a concentration-dependent and reversible manner. The relaxant effect of F3–5 (100 μg ml−1) on phenylephrine contraction was unaffected in the presence of atropine, N-ω-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one and by preincubation with tetrodotoxin, glibenclamide, apamine and charybdotoxin suggesting that mechanisms other than cholinergic, nitrergic, sGC activation or potassium channel opening are probably involved. However, the phasic component of the contraction induced by K+ 60 mM as well as the maximal contraction elicited by increasing external Ca2+ concentrations in depolarized corpora cavernosa was inhibited by F3–5. We conclude that F3–5 relaxes the RbCC smooth muscle, at least in part, through a blockade of calcium influx or its function.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 8 print issues and online access
$259.00 per year
only $32.38 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Maggi M, Filippi S, Ledda F, Magini A, Forti G . Erectile dysfunction: from biochemical pharmacology to advances in medical therapy. Eur J Endocrinol 2000; 143: 143–154.
Giuliano F, Bernabe J, Alexandre L, Niewoehner U, Haning H, Bischoff E . Pro-erectile effect of vardenafil: in vitro experiments in rabbits and in vivo comparison with sildenafil in rats. Eur Urol 2003; 44: 731–736.
Ignarro LJ . Nitric oxide. A novel signal transduction mechanism for transcellular communication. Hypertension 1990; 16: 477–483.
Lue TF . Erectile dysfunction. New Engl J Med 2000; 342: 1802–1813.
Bischoff E . Vardenafil preclinical trial data: potency, pharmacodynamics, pharmacokinetics, and adverse events. Int J Impot Res 2004; 16 (Suppl 1): S34–S37.
Carson CC . Erectile dysfunction: evaluation and new treatment options. Psychosom Med 2004; 66: 664–671.
Guirguis WR . Oral treatment of erectile dysfunction: from herbal remedies to designer drugs. J Sex Marital Ther 1998; 24: 69–73.
Harvey AL . Medicines from nature: are natural products still relevant to drug discovery? Trends Pharmacol Sci 1999; 20: 196–198.
Cícero AF, Bandieri E, Arletti R . Lepidium meyenii Walp. improves sexual behaviour in male rats independently from its action on spontaneous locomotor activity. J Ethnopharmacol 2001; 75: 225–229.
Drewes SE, George J, Khan F . Recent findings on natural products with erectile-dysfunction activity. Phytochemistry 2003; 62: 1019–1025.
Zaher TF . Papaverine plus PGE, versus PG E1 alone for intracorporeal injection therapy. Intl Urol Nephrol 1998; 30: 193–196.
Matsumoto K, Yoshida M, Andersson KE, Hedlund P . Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum. Br J Pharmacol 2005; 146: 259–267.
Chiou WF, Chen J, Chen CF . Relaxation of corpus cavernosum and raised intracavernous pressure by berberine in rabbit. Br J Pharmacol 1998; 125: 1677–1684.
Dinsmore WW . Available and future treatments for erectile dysfunction. Clin Cornerstone 2005; 7: 37–45.
Deutsch HF, Evenson MA, Drescher P, Sparwasser C, Madsen PO . Isolation and biological activity of aspidospermine and quebrachamine from Aspidosperma tree source. J Pharmaceut Biomed Anal 1994; 12: 1283–1287.
Pereira MM, Jacome RL, Alcântara AF, Alves RB, Raslan DS . Alcalóides indólicos isolados de espécies do gênero Aspidosperma (Apocynaceae). Quim Nova 2007; 30: 970–983.
Tanaka JCA, da Silva CC, de Oliveira AIB, Nakamura CV, Dias Filho BP . Antibacterial activity of índole alkaloids from Aspidosperma ramiflorum. Braz J Med Biol Res 2006; 3: 387–391.
Weniger B, Robledo S, Arango GJ, Deharo E, Aragon R, Munoz V et al. Antiprotozoal activities of Colombian J plants. J Ethnopharmacol 2001; 78: 193–200.
Lyon RL, Fong HH, Farnsworth NR, Svoboda GH . Biological and phytochemical evaluation of plants. XI. Isolation of aspidospermine, quebrachidine, rhazinilam, (−)-pyrifolidine, and akuammidine from Aspidosperma quebracho-blanco (Apocynaceae). J Pharm Sci 1973; 62: 218–221.
Sperling H, Lorenz A, Krege S, Arndt R, Michel MC . An extract from the bark of Aspidosperma quebracho-blanco binds to human penile alpha-adrenoceptors. J Urol 2002; 168: 160–163.
Guay AT, Spark RF, Jacobson J, Murray FT, Giesser ME . Yohimbine treatment of organic erectile dysfunction. Int J Impot Res 2002; 14: 25–31.
Banerjee JN, Lewis JJ . Pharmacological studies in the Apocyanaceous genus Aspidiosperma Mart. Zucc., Aspidiosperma ulei MGF. J Pharm Pharmacol 1955; 7: 42–45.
Campos AR, Lima Júnior RCP, Uchoa DEA, Silveira ER, Santos FA, Rao VS . Pro-erectile effects of an alkaloidical rich fraction from Aspidosperma ulei root bark in mice. J Ethnopharmacol 2006; 104: 240–244.
Staerk D, Norrby PO, Jaroszewski JW . Conformational analysis of indole alkaloids corynantheine and dihydrocorynantheine by dynamic 1H NMR spectroscopy and computational methods: steric effects of ethyl vs vinyl group. J Org Chem 2001; 66: 2217–2221.
Yildirim S, Simsek R, Ayan S, Gokce G, Sarioglu Y, Safak C . Relaxant effects of some benzothiazolinone derivatives on isolated rabbit corpus cavernosum. Urol Res 2001; 29: 182–185.
Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, Rajfer J . Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 1990; 170: 843–850.
Williams BA, Liu C, De Young L, Brock GB, Sims SM . Regulation of intracellular Ca+2 release in corpus cavernosum smooth muscle: synergism between nitric oxide and cGMP. Am J Physiol Cell Physiol 2005; 88: C650–C658.
Teixeira CE, Faro R, Moreno RA, Netto Jr N, Fregonesi A, Antunes E et al. Nonadrenergic, noncholinergic relaxation of human isolated corpus cavernosum induced by scorpion venom. Urology 2001; 7: 816–820.
Lin RJ, Wu BN, Shen KP, Lo YT, Huang CH, Chen IJ . KMUP-1 relaxes rabbit corpus cavernosum smooth muscle in vitro and in vivo: involvement of cyclic GMP and K+ channels. Br J Pharmacol 2002; 135: 1159–1166.
Wang HZ, Lee SW, Christ GJ . Comparative studies of the maxi-K (KCa) channel in freshly isolated myocytes in human and rat corpora. Int J Impot Res 2000; 12: 9–18.
Archer SL . Potassium channels and erectile dysfunction. Vasc Pharmacol 2002; 38: 61–71.
Takahashi R, Nishimura J, Hirano K, Naito S, Kanaide H . Modulation of Ca+2 sensitivity regulates contractility of rabbit corpus cavernosum smooth muscle. J Urol 2003; 169: 2412–2428.
Gonzalez-Cadavid NF, Rajfer J . Therapeutic stimulation of penile nitric oxide synthase (NOS) and related pathways. Drugs Today (Barc) 2000; 36: 163–174.
Rembold CM . Electromechanical and pharmacomechanical coupling. In: Barany M (ed). Biochemistry of Smooth Muscle Contraction. Academic Press: San Diego, 1996, pp 227–239.
Acknowledgements
This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, proc. no. 472717/2003-0), and Fundação Cearense de Pesquisa e Cultura (FUNCAP, proc. no. 30/2002).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Campos, A., Cunha, K., Santos, F. et al. Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on isolated rabbit corpus cavernosum. Int J Impot Res 20, 255–263 (2008). https://doi.org/10.1038/sj.ijir.3901624
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijir.3901624
Keywords
This article is cited by
-
Relaxant effect and possible mechanism of 17-nor-subincanadine E in rabbit corpora cavernosa
Asian Journal of Andrology (2011)
-
Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits
International Journal of Impotence Research (2010)
-
Yohimbine relaxes the human corpus cavernosum through a non-adrenergic mechanism involving the activation of K+ATP-dependent channels
International Journal of Impotence Research (2009)