Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Nov;110(3):943–948. doi: 10.1111/j.1476-5381.1993.tb13904.x

Study of the mechanism of the relaxant action of (+)-glaucine in rat vas deferens.

F Orallo 1, A Fernández Alzueta 1, M I Loza 1, N Vivas 1, A Badía 1, M Campos 1, M A Honrubia 1, M I Cadavid 1
PMCID: PMC2175806  PMID: 8298818

Abstract

1. Effects of the aporphinoid alkaloid, (+)-glaucine, on rat vas deferens were investigated. 2. (+)-Glaucine (2-18 microM) competitively inhibited contractions induced by noradrenaline and methoxamine with a pA2 value of about 6. 3. (+)-Glaucine (2 and 18 microM) did not change the accumulation of tritium during incubation of the vas deferens with [3H]-noradrenaline. 4. (+)-Glaucine (0.3 nM-0.1 mM) inhibited specific [3H]-prazosin binding to membranes from rat vas deferens with a pKi value of 6.63, which is close to the pA2 value obtained against noradrenaline and methoxamine in functional studies. 5. In electrically-stimulated rat vas deferens, (+)-glaucine (0.3-10 microM) enhanced twitch contractions and competitively antagonized the inhibitory effect of clonidine with a pA2 value of 5.91. 6. In tissues incubated in depolarizing calcium-free high-potassium medium, (+)-glaucine (30-80 microM) inhibited Ca(2+)-induced contractions with depression of the maximal response at higher doses and with a pD'2 value of 3.65. Furthermore, (+)-glaucine (50 microM) did not modify basal 45Ca uptake but strongly inhibited the influx of 45Ca induced by K+. 7. These results suggest that (+)-glaucine has non-selective alpha 1- and alpha 2-adrenoceptor blocking properties. At higher doses, (+)-glaucine shows calcium antagonist activity which may be responsible, at least in part, for the inhibition of the contractions induced by Ca2+ in calcium-free high-potassium medium.

Full text

PDF
943

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anselmi E., Fayos G., Blasco R., Candenas L., Cortes D., D'Ocon P. Selective inhibition of calcium entry induced by benzylisoquinolines in rat smooth muscle. J Pharm Pharmacol. 1992 Apr;44(4):337–343. doi: 10.1111/j.2042-7158.1992.tb03617.x. [DOI] [PubMed] [Google Scholar]
  3. Berthe J., Remandet B., Mazue G., Tilson H. A. Neurobehavioral effects of D-glaucine in rats. Neurobehav Toxicol Teratol. 1983 May-Jun;5(3):305–308. [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  5. Cheng Y., Prusoff W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 1973 Dec 1;22(23):3099–3108. doi: 10.1016/0006-2952(73)90196-2. [DOI] [PubMed] [Google Scholar]
  6. Clapham J. C., Wilson C. Anti-spasmogenic and spasmolytic effects of BRL 34915: a comparison with nifedipine and nicorandil. J Auton Pharmacol. 1987 Sep;7(3):233–242. doi: 10.1111/j.1474-8673.1987.tb00152.x. [DOI] [PubMed] [Google Scholar]
  7. Cortes D., Torrero M. Y., Pilar D'Ocon M., Luz Candenas M., Cavé A., Hadi A. H. Norstephalagine et atherospermidine, deux aporphines d'Artabotrys maingayi relaxantes du muscle lisse. J Nat Prod. 1990 Mar-Apr;53(2):503–508. doi: 10.1021/np50068a039. [DOI] [PubMed] [Google Scholar]
  8. Doxey J. C., Smith C. F., Walker J. M. Selectivity of blocking agents for pre-and postsynaptic alpha-adrenoceptors. Br J Pharmacol. 1977 May;60(1):91–96. doi: 10.1111/j.1476-5381.1977.tb16752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drew G. M. Pharmacological characterisation of the presynaptic alpha-adrenoceptor in the rat vas deferens. Eur J Pharmacol. 1977 Mar 21;42(2):123–130. doi: 10.1016/0014-2999(77)90351-x. [DOI] [PubMed] [Google Scholar]
  10. Gross G., Hanft G., Rugevics C. U. Alpha 1-adrenoceptors of rat myocardium: comparison of agonist binding and positive inotropic response. Naunyn Schmiedebergs Arch Pharmacol. 1988 Nov;338(5):582–588. doi: 10.1007/BF00179334. [DOI] [PubMed] [Google Scholar]
  11. Hamilton T. C., Weir S. W., Weston A. H. Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol. 1986 May;88(1):103–111. doi: 10.1111/j.1476-5381.1986.tb09476.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hanft G., Gross G., Beckeringh J. J., Korstanje C. Alpha 1-adrenoceptors: the ability of various agonists and antagonists to discriminate between two distinct [3H]prazosin binding sites. J Pharm Pharmacol. 1989 Oct;41(10):714–716. doi: 10.1111/j.2042-7158.1989.tb06348.x. [DOI] [PubMed] [Google Scholar]
  13. Hanft G., Gross G. Subclassification of alpha 1-adrenoceptor recognition sites by urapidil derivatives and other selective antagonists. Br J Pharmacol. 1989 Jul;97(3):691–700. doi: 10.1111/j.1476-5381.1989.tb12005.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ivorra M. D., Lugnier C., Schott C., Catret M., Noguera M. A., Anselmi E., D'Ocon P. Multiple actions of glaucine on cyclic nucleotide phosphodiesterases, alpha 1-adrenoceptor and benzothiazepine binding site at the calcium channel. Br J Pharmacol. 1992 Jun;106(2):387–394. doi: 10.1111/j.1476-5381.1992.tb14345.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jurkiewicz A., Jurkiewicz N. H. Dual effect of alpha-adrenoceptor antagonists in rat isolated vas deferens. Br J Pharmacol. 1976 Feb;56(2):169–178. doi: 10.1111/j.1476-5381.1976.tb07439.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kasé Y., Kawaguchi M., Takahama K., Miyata T., Hirotsu I., Hitoshi T., Okano Y. Pharmacological studies on dl-glaucine phosphate as an antitussive. Arzneimittelforschung. 1983;33(7):936–946. [PubMed] [Google Scholar]
  17. MacDonald A., McGrath J. C. The distribution of adrenoceptors and other drug receptors between the two ends of the rat vas deferens as revealed by selective agonists and antagonists. Br J Pharmacol. 1980;71(2):445–458. doi: 10.1111/j.1476-5381.1980.tb10957.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mallard N. J., Marshall R. W., Sithers A. J., Spriggs T. L. Separation of putative alpha 1A- and alpha 1B-adrenoceptor mediated components in the tension response of the rat vas deferens to electrical field stimulation. Br J Pharmacol. 1992 Mar;105(3):727–731. doi: 10.1111/j.1476-5381.1992.tb09046.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morrow A. L., Creese I. Characterization of alpha 1-adrenergic receptor subtypes in rat brain: a reevaluation of [3H]WB4104 and [3H]prazosin binding. Mol Pharmacol. 1986 Apr;29(4):321–330. [PubMed] [Google Scholar]
  20. Petkov V., Stancheva S. In vitro inhibition of cyclic 3' 5',-AMP-phosphodiesterase by a group of structural analogues of glaucine. Acta Physiol Pharmacol Bulg. 1980;6(3):38–47. [PubMed] [Google Scholar]
  21. Petkov V., Todorov S., Georgiev V., Petkova B., Donev N. Pharmacological studies of a group of semi-synthetic structural analogues of glaucine. Acta Physiol Pharmacol Bulg. 1979;5(4):3–12. [PubMed] [Google Scholar]
  22. Roquebert J., Gomond P., Demichel P. Activité antinoradrénergique de la raubasine sur l'aorte thoracique et le canal déférent isolés de rat. J Pharmacol. 1981 Nov-Dec;12(4):393–403. [PubMed] [Google Scholar]
  23. Sallés J., Badia A. Mechanisms underlying the differential sensitivity to alpha 1-adrenoceptor activation in the bisected rat vas deferens. Br J Pharmacol. 1991 Feb;102(2):439–445. doi: 10.1111/j.1476-5381.1991.tb12192.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Smith K., Docherty J. R. Are the prejunctional alpha 2-adrenoceptors of the rat vas deferens and submandibular gland of the alpha 2A- or alpha 2D-subtype? Eur J Pharmacol. 1992 Aug 25;219(2):203–210. doi: 10.1016/0014-2999(92)90297-h. [DOI] [PubMed] [Google Scholar]
  25. Starke K., Endo T., Taube H. D. Relative pre- and postsynaptic potencies of alpha-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn Schmiedebergs Arch Pharmacol. 1975;291(1):55–78. doi: 10.1007/BF00510821. [DOI] [PubMed] [Google Scholar]
  26. VAN ROSSUM J. M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther. 1963;143:299–330. [PubMed] [Google Scholar]
  27. van Breemen C., Saida K. Cellular mechanisms regulating [Ca2+]i smooth muscle. Annu Rev Physiol. 1989;51:315–329. doi: 10.1146/annurev.ph.51.030189.001531. [DOI] [PubMed] [Google Scholar]
  28. von Kügelgen I., Starke K. Noradrenaline-ATP co-transmission in the sympathetic nervous system. Trends Pharmacol Sci. 1991 Sep;12(9):319–324. doi: 10.1016/0165-6147(91)90587-i. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES