Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1985 May;85(1):189–195. doi: 10.1111/j.1476-5381.1985.tb08846.x

Ketamine-inhibition of calcium-induced contractions in depolarized rat uterus: a comparison with other calcium antagonists.

J B Calixto, S Loch
PMCID: PMC1916754  PMID: 4027464

Abstract

The inhibitory effect of the intravenous anaesthetic ketamine on CaCl2-induced contractions in the isolated K+-depolarized uterus of the rat in Ca2+-free medium was compared with that produced by papaverine, theophylline and the calcium entry blocker verapamil. Pre-incubation for 20 min with either ketamine (0.3 to 3 mM), papaverine (3 to 30 microM), theophylline (0.1 to 1 mM) or verapamil (3 to 30 nM) induced parallel, concentration-dependent rightward displacements of the dose-response curves to Ca2+ (0.04 to 22 mM). The antagonism was competitive, except that due to verapamil, the Schild plot for which yielded a slope which differed significantly from unity. The calculated pA2 values (+/- s.e.mean) were: ketamine 3.90 +/- 0.07; papaverine 5.55 +/- 0.05; theophylline 3.99 +/- 0.1 and verapamil 9.54 +/- 0.24. These drugs differed in their ability to relax the sustained contraction induced by Ca2+ (1 mM) in K+-depolarizing solution. Ketamine and verapamil relaxed the preparation in a concentration-dependent manner whereas theophylline and especially papaverine were less potent and induced only partial maximal relaxation. The t1/2 of the relaxant effect was significantly less for ketamine than for verapamil (5 and 22 min, respectively). Only ketamine produced a relaxation comparable to that obtained by washing the preparation with Ca2+-free solution (t1/2 = approx. 5 min). Prior exposure of the depolarized uterine strip to a low concentration of Ca2+ (0.22 mM) increased the potency of ketamine, but decreased that of papaverine and theophylline, in antagonizing Ca2+ induced contractions. In contrast, this procedure did not affect the potency of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
189

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. Altura B. M., Altura B. T., Carella A. Effects of ketamine on vascular smooth muscle function. Br J Pharmacol. 1980 Oct;70(2):257–267. doi: 10.1111/j.1476-5381.1980.tb07931.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Calixto J. B., Aucélio J. G., Duarte D. F. Inhibitory effects of ketamine on the isolated uteri of the rat: evidence for the mechanism of action. Can J Physiol Pharmacol. 1983 Nov;61(11):1305–1311. doi: 10.1139/y83-188. [DOI] [PubMed] [Google Scholar]
  4. Clanachan A. S., McGrath J. C. Effects of ketamine on the peripheral autonomic nervous system of the rat. Br J Pharmacol. 1976 Oct;58(2):247–252. doi: 10.1111/j.1476-5381.1976.tb10402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen M. L., Chan S. L., Way W. L., Trevor A. J. Distribution in the brain and metabolism of ketamine in the rat after intravenous administration. Anesthesiology. 1973 Oct;39(4):370–376. doi: 10.1097/00000542-197310000-00003. [DOI] [PubMed] [Google Scholar]
  6. Cohen M. L., Trevor A. J. On the cerebral accumulation of ketamine and the relationship between metabolism of the drug and its pharmacological effects. J Pharmacol Exp Ther. 1974 May;189(2):351–358. [PubMed] [Google Scholar]
  7. Fukuda S., Murakawa T., Takeshita H., Toda N. Direct effects of ketamine on isolated canine cerebral and mesenteric arteries. Anesth Analg. 1983 Jun;62(6):553–558. [PubMed] [Google Scholar]
  8. Godfraind T., Kaba A., Polster P. Differences in sensitivity of arterial smooth muscles to inhibition of their contractile response to depolarization by potassium. Arch Int Pharmacodyn Ther. 1968 Mar;172(1):235–239. [PubMed] [Google Scholar]
  9. Hof R. P., Vuorela H. J. Assessing calcium antagonism on vascular smooth muscle: a comparison of three methods. J Pharmacol Methods. 1983 Feb;9(1):41–52. doi: 10.1016/0160-5402(83)90049-9. [DOI] [PubMed] [Google Scholar]
  10. Huddart H., Bayton E., Shanklin J. Influence of some common methylxanthines on contractile responses and calcium mobilization of ileal, vas deferens and bladder smooth muscle. J Exp Biol. 1983 Nov;107:73–93. doi: 10.1242/jeb.107.1.73. [DOI] [PubMed] [Google Scholar]
  11. Huddart H., Langton P. D., Saad K. H. Inhibition by papaverine of calcium movements and tension in the smooth muscles of rat vas deferens and urinary bladder. J Physiol. 1984 Apr;349:183–194. doi: 10.1113/jphysiol.1984.sp015151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Imai S., Kitagawa T. A comparison of the differential effects of nitroglycerin, nifedipine and papaverine on contractures induced in vascular and intestinal smooth muscle by potassium and lanthanum. Jpn J Pharmacol. 1981 Apr;31(2):193–199. doi: 10.1254/jjp.31.193. [DOI] [PubMed] [Google Scholar]
  13. Koike K., Takayanagi I. Possible mechanisms of stimulatory action of papaverine on calcium-uptake by rat uterine microsomal fraction. Jpn J Pharmacol. 1981 Oct;31(5):757–762. doi: 10.1254/jjp.31.757. [DOI] [PubMed] [Google Scholar]
  14. Little H. J., Alexander K. L., Gargan M. F., Widdison A. L. Ketamine and the guinea-pig ileum: possible opiate agonist and antagonist actions and effects of peptidase inhibition. J Pharmacol Exp Ther. 1983 Apr;225(1):206–212. [PubMed] [Google Scholar]
  15. Lundy P. M., Gowdey C. W., Colhoun E. H. Further experimental evidence for a smooth muscle depressant effect of ketamine. Arch Int Pharmacodyn Ther. 1975 Jul;216(1):57–62. [PubMed] [Google Scholar]
  16. Lundy P. M., Gowdey C. W., Colhoun E. H. Tracheal smooth muscle relaxant effect of ketamine. Br J Anaesth. 1974 May;46(5):333–336. doi: 10.1093/bja/46.5.333. [DOI] [PubMed] [Google Scholar]
  17. Ohashi M., Takayanagi I. The actions of D 600, aspaminol and papaverine on calcium-, potassium- and histamine-induced contractions of isolated rabbit basilar artery, aorta, taenia coli and tracheal smooth muscle. Jpn J Pharmacol. 1983 Dec;33(6):1135–1144. doi: 10.1254/jjp.33.1135. [DOI] [PubMed] [Google Scholar]
  18. Saida K., van Breemen C. Mechanism of Ca++ antagonist-induced vasodilation. Intracellular actions. Circ Res. 1983 Feb;52(2):137–142. doi: 10.1161/01.res.52.2.137. [DOI] [PubMed] [Google Scholar]
  19. Spedding M. Assessment of "Ca2+ -antagonist" effects of drugs in K+ -depolarized smooth muscle. Differentiation of antagonist subgroups. Naunyn Schmiedebergs Arch Pharmacol. 1982 Feb;318(3):234–240. doi: 10.1007/BF00500485. [DOI] [PubMed] [Google Scholar]
  20. Spedding M. Direct inhibitory effects of some 'calcium-antagonists' and trifluoperazine on the contractile proteins in smooth muscle. Br J Pharmacol. 1983 May;79(1):225–231. doi: 10.1111/j.1476-5381.1983.tb10516.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Takayanagi I., Hisayama T., Suzuki S. Effects of nonspecific smooth muscle relaxants and Ca-blocker on Ca-release and Ca-binding in microsomal fractions from rabbit taenia coli. Jpn J Pharmacol. 1980 Oct;30(5):641–646. doi: 10.1254/jjp.30.641. [DOI] [PubMed] [Google Scholar]
  22. Thorens S., Haeusler G. Effects of some vasodilators on calcium translocation in intact and fractionated vascular smooth muscle. Eur J Pharmacol. 1979 Feb 15;54(1-2):79–91. doi: 10.1016/0014-2999(79)90410-2. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Van Breemen C. Calcium requirement for activation of intact aortic smooth muscle. J Physiol. 1977 Nov;272(2):317–329. doi: 10.1113/jphysiol.1977.sp012046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weiss B., Hait W. N. Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents. Annu Rev Pharmacol Toxicol. 1977;17:441–477. doi: 10.1146/annurev.pa.17.040177.002301. [DOI] [PubMed] [Google Scholar]

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

RESOURCES