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. 1975 Feb;53(2):279–285. doi: 10.1111/j.1476-5381.1975.tb07359.x

Studies on the mechanism of action of a new Ca-2+ antagonist, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride in smooth and skeletal muscles.

C Y Chiou, M H Malagodi
PMCID: PMC1666297  PMID: 1148488

Abstract

1. The rabbit aortic strip, guinea-pig ileum and rabbit skeletal muscle sarcoplasmic reticulum preparations were used to determine at which sites and in what manner 8-(N,N-diethylamino)-octyl 3,4,5,-trimethoxybenzoate (TMB-8) interferes with Ca2+ availability in smooth and skeletal muscles. 2. TMB-8 (50 muM) significantly inhibited equivalent responses of the rabbit aortic strip to KCl and noradrenaline. 3. TMB-8 (65 muM) produced no significant alteration in the extracellular space of the guinea-pig ileum as measured with [3H]-sorbitol. 4. The resting cellular Ca2+ influx as well as the resting 45Ca2+ efflux in the guinea-pig ileum preparation were significantly inhibited by TMB-8 (65 muM). 5. TMB-8 (5 muM and 50 muM) had no significant effect on the uptake of 45Ca2+ by the sarcoplasmic reticulum preparation of skeletal muscle; however, TMB-8 (5 muM) did significantly inhibit the caffeine (20 mM)-induced release of 45Ca2+ from this preparation. 6. It is concluded that TMB-8 reduces Ca2+ availability in smooth and skeletal muscles by stabilizing Ca2+ binding to cellular Ca2+ stores and thereby inhibits the release of this Ca2+ by contractile stimuli.

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Selected References

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

  1. Antonio A., Rocha e Silva M., Yashuda Y. The tachyphylactic effect of barium on intestinal smooth muscle. Arch Int Pharmacodyn Ther. 1973 Aug;204(2):260–267. [PubMed] [Google Scholar]
  2. CALDWELL P. C., WALSTER G. STUDIES ON THE MICRO-INJECTION OF VARIOUS SUBSTANCES INTO CRAB MUSCLE FIBRES. J Physiol. 1963 Nov;169:353–372. doi: 10.1113/jphysiol.1963.sp007261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ebashi S., Endo M. Calcium ion and muscle contraction. Prog Biophys Mol Biol. 1968;18:123–183. doi: 10.1016/0079-6107(68)90023-0. [DOI] [PubMed] [Google Scholar]
  4. Ebashi S., Endo M., Otsuki I. Control of muscle contraction. Q Rev Biophys. 1969 Nov;2(4):351–384. doi: 10.1017/s0033583500001190. [DOI] [PubMed] [Google Scholar]
  5. Godfraind T., Kaba A. Actions phasique et tonique de l'adrénaline sur un muscle lisse vasculaire et leur inhibition par des agents pharmacologiques. Arch Int Pharmacodyn Ther. 1969 Apr;178(2):488–491. [PubMed] [Google Scholar]
  6. Haeusler G. Differential effect of verapamil on excitation-contraction coupling in smooth muscle and on excitation-secretion coupling in adrenergic nerve terminals. J Pharmacol Exp Ther. 1972 Mar;180(3):672–682. [PubMed] [Google Scholar]
  7. Holman M. E. A discussion on recent developments in vertebrate smooth muscle physiology. A survey of new findings and the discussions arising during sessions I. II and 3. Philos Trans R Soc Lond B Biol Sci. 1973 Mar 15;265(867):157–165. doi: 10.1098/rstb.1973.0018. [DOI] [PubMed] [Google Scholar]
  8. Hudgins P. M., Weiss G. B. Differential effects of calcium removal upon vascular smooth muscle contraction induced by norepinephrine, histamine and potassium. J Pharmacol Exp Ther. 1968 Jan;159(1):91–97. [PubMed] [Google Scholar]
  9. Karaki H., Ikeda M., Urakawa N. Effects of external calcium and some metabolic inhibitors on barium-induced tension changes in guinea pig taenia coli. Jpn J Pharmacol. 1967 Dec;17(4):603–612. doi: 10.1254/jjp.17.603. [DOI] [PubMed] [Google Scholar]
  10. Malagodi M. H., Chiou C. Y. Pharmacological evaluation of a new Ca++ antagonist, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8): studies in skeletal muscles. Pharmacology. 1974;12(1):20–31. doi: 10.1159/000136517. [DOI] [PubMed] [Google Scholar]
  11. Malagodi M. H., Chiou C. Y. Pharmacological evaluation of a new Ca2+ antagonist, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8): studies in smooth muscles. Eur J Pharmacol. 1974 Jun;27(1):25–33. doi: 10.1016/0014-2999(74)90198-8. [DOI] [PubMed] [Google Scholar]
  12. Nayler W. G. Influx and efflux of calcium in the physiology of muscle contraction. Clin Orthop Relat Res. 1966 May-Jun;46:157–182. [PubMed] [Google Scholar]
  13. Saito Y., Sakai Y., Urakawa N. Effect of cholinergic drugs and barium on oxygen consumption in guinea pig taenia coli. Jpn J Pharmacol. 1972 Oct;22(5):653–661. doi: 10.1254/jjp.22.653. [DOI] [PubMed] [Google Scholar]
  14. Scarpa A., Baldassare J., Inesi G. The effect of calcium ionophores on fragmented sarcoplasmic reticulum. J Gen Physiol. 1972 Dec;60(6):735–749. doi: 10.1085/jgp.60.6.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Somlyo A. P. Excitation-contraction coupling in vertebrate smooth muscle: correlation of ultrastructure with function. Physiologist. 1972 Nov;15(4):338–348. [PubMed] [Google Scholar]
  16. Thorpe W. R., Seeman P. The site of action of caffeine and procaine in skeletal muscle. J Pharmacol Exp Ther. 1971 Nov;179(2):324–330. [PubMed] [Google Scholar]
  17. Thorpe W. R. Some effects of caffeine and quinidine on sarcoplasmic reticulum of skeletal and cardiac muscle. Can J Physiol Pharmacol. 1973 Jul;51(7):499–503. doi: 10.1139/y73-073. [DOI] [PubMed] [Google Scholar]
  18. Weber A., Herz R. The relationship between caffeine contracture of intact muscle and the effect of caffeine on reticulum. J Gen Physiol. 1968 Nov;52(5):750–759. doi: 10.1085/jgp.52.5.750. [DOI] [PMC free article] [PubMed] [Google Scholar]

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