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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1979 Aug;66(4):591–600. doi: 10.1111/j.1476-5381.1979.tb13699.x

Effects of methoxyverapamil on the stimulation by Ca2+, Sr2+ and Ba2+ and on the inhibition by Mg2+ of catecholamine release from the adrenal medulla.

J Aguirre, J Falutz, J E Pinto, J M Trifaró
PMCID: PMC2043585  PMID: 465897

Abstract

1 Bovine adrenal glands were perfused with Ca2+-free Locke solution and catecholamine release was induced either by the introduction of Ca2+, Sr2+ or Ba2+ into the perfusion fluid or by the substitution of Na+ by an osmotically equivalent amount of sucrose. 2 Methoxyverapamil (D600) at a concentration of 3 X 10(-4) M blocked the release of catecholamines in response to Ca2+, Sr2+ or Ba2+ stimulation but failed to block the release evoked by the omission of Na+. 3 Mg2+ (10 to 20 mM) blocked the release induced by Na+-deprivation; however, this inhibitory effect of Mg2+ was not modified by D600. 4 D600 blocked the increase in the efflux of 45Ca from the perfused gland induced by the introduction of Ca2+ into the perfusion fluid and blocked the uptake of 45Ca into adrenal medullary slices induced by K+ depolarization. 5 The results suggest that Ca2+, Sr2+ and Ba2+ may enter the chromaffin cell through the same channel and that this channel is blocked by D600. Mg2+ may enter the cell through the same Ca2+ channel but with a high rate of permeation or it may enter through a channel which is resistant to D600. Alternatively, Mg2+ may exert this inhibitory effect at an extracellular site.

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Selected References

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  1. ANTON A. H., SAYRE D. F. A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines. J Pharmacol Exp Ther. 1962 Dec;138:360–375. [PubMed] [Google Scholar]
  2. Aguirre J., Pinto J. E., Trifaró J. M. Calcium movements during the release of catecholamines from the adrenal medulla: effects of methoxyverapamil and external cations. J Physiol. 1977 Jul;269(2):371–394. doi: 10.1113/jphysiol.1977.sp011907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ashley C. C., Ellory J. C. The efflux of magnesium from single crustacean muscle fibres. J Physiol. 1972 Nov;226(3):653–674. doi: 10.1113/jphysiol.1972.sp010002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Atwater I., Biegelman P. M., Ribalet B. Three actions of Ba2+ upon membrane potential in mouse pancreatic beta-cells [proceedings]. J Physiol. 1977 Mar;266(1):38P–39P. [PubMed] [Google Scholar]
  5. Baker P. F., Crawford A. C. Mobility and transport of magnesium in squid giant axons. J Physiol. 1972 Dec;227(3):855–874. doi: 10.1113/jphysiol.1972.sp010062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Baker P. F., Meves H., Ridgway E. B. Calcium entry in response to maintained depolarization of squid axons. J Physiol. 1973 Jun;231(3):527–548. doi: 10.1113/jphysiol.1973.sp010247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Baker P. F., Rink T. J. Catecholamine release from bovine adrenal medulla in response to maintained depolarization. J Physiol. 1975 Dec;253(2):593–620. doi: 10.1113/jphysiol.1975.sp011209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Buchs M., Dreifuss J. J., Grau J. D., Nordmann J. J. Strontium as a substitute for calcium in the process leading to neurohypophysial hormone secretion. J Physiol. 1972 Apr;222(2):168P–169P. [PubMed] [Google Scholar]
  9. DOUGLAS W. W., POISNER A. M. On the mode of action of acetylcholine in evoking adrenal medullary secretion: increased uptake of calcium during the secretory response. J Physiol. 1962 Aug;162:385–392. doi: 10.1113/jphysiol.1962.sp006940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DOUGLAS W. W., RUBIN R. P. STIMULANT ACTION OF BARIUM ON THE ADRENAL MEDULLA. Nature. 1964 Jul 18;203:305–307. doi: 10.1038/203305a0. [DOI] [PubMed] [Google Scholar]
  11. DOUGLAS W. W., RUBIN R. P. THE EFFECTS OF ALKALINE EARTHS AND OTHER DIVALENT CATIONS ON ADRENAL MEDULLARY SECRETION. J Physiol. 1964 Dec;175:231–241. doi: 10.1113/jphysiol.1964.sp007514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DOUGLAS W. W., RUBIN R. P. The role of calcium in the secretory response of the adrenal medulla to acetylcholine. J Physiol. 1961 Nov;159:40–57. doi: 10.1113/jphysiol.1961.sp006791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dodge F. A., Jr, Miledi R., Rahamimoff R. Strontium and quantal release of transmitter at the neuromuscular junction. J Physiol. 1969 Jan;200(1):267–283. doi: 10.1113/jphysiol.1969.sp008692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Douglas W. W., Kanno T., Sampson S. R. Influence of the ionic environment on the membrane potential of adrenal chromaffin cells and on the depolarizing effect of acetylcholine. J Physiol. 1967 Jul;191(1):107–121. doi: 10.1113/jphysiol.1967.sp008239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Douglas W. W. Stimulus-secretion coupling: the concept and clues from chromaffin and other cells. Br J Pharmacol. 1968 Nov;34(3):451–474. doi: 10.1111/j.1476-5381.1968.tb08474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dreifuss J. J., Grau J. D., Nordmann J. J. Effects on the isolated neurohypophysis of agents which affect the membrane permeability to calcium. J Physiol. 1973 Jun;231(2):96P–98P. [PMC free article] [PubMed] [Google Scholar]
  17. Fleckenstein A., Grün G., Tritthart H., Byon K. Uterus-Relaxation durch hochaktive Ca plus,plus-antagonistische Hemmstoffe der elektro-mechanischen Koppelung wie Isoptin (Verapamil, Iproveratril), Substanz D 600 und Segontin (Prenylamin). Versuche am isolierten Uterus virgineller Ratten. Klin Wochenschr. 1971 Jan;49(1):32–41. doi: 10.1007/BF01494064. [DOI] [PubMed] [Google Scholar]
  18. Foreman J. C., Mongar J. L. Proceedings: Activation of anaphylactic histamine release by calcium and strontium ions. Br J Pharmacol. 1972 Feb;44(2):326P–326P. [PMC free article] [PubMed] [Google Scholar]
  19. Kohlhardt M., Bauer B., Krause H., Fleckenstein A. Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibres by the use of specific inhibitors. Pflugers Arch. 1972;335(4):309–322. doi: 10.1007/BF00586221. [DOI] [PubMed] [Google Scholar]
  20. Lastowecka A., Trifaró J. M. The effect of sodium and calcium ions on the release of catecholamines from the adrenal medulla: sodium deprivation induces release by exocytosis in the absence of extracellular calcium. J Physiol. 1974 Feb;236(3):681–705. doi: 10.1113/jphysiol.1974.sp010460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Meiri U., Rahamimoff R. Activation of transmitter release by strontium and calcium ions at the neuromuscular junction. J Physiol. 1971 Jul;215(3):709–726. doi: 10.1113/jphysiol.1971.sp009493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pinto J. E., Trifaró J. M. The different effects of D-600 (methoxyverapamil) on the release of adrenal catecholamines induced by acetylcholine, high potassium or sodium deprivation. Br J Pharmacol. 1976 May;57(1):127–132. doi: 10.1111/j.1476-5381.1976.tb07662.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Poisner A. M., Hava M. The role of adenosine triphosphate and adenosine triphosphatase in the release of catecholamines from the adrenal medulla. IV. Adenosine triphosphate-- activated uptake of calcium by microsomes and mitochondria. Mol Pharmacol. 1970 Jul;6(4):407–415. [PubMed] [Google Scholar]
  24. Rink T. J. The influence of sodium on calcium movements and catecholamine release in thin slices of bovine adrenal medulla. J Physiol. 1977 Apr;266(2):297–325. doi: 10.1113/jphysiol.1977.sp011769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rojas E., Taylor R. E. Simultaneous measurements of magnesium, calcium and sodium influxes in perfused squid giant axons under membrane potential control. J Physiol. 1975 Oct;252(1):1–27. doi: 10.1113/jphysiol.1975.sp011131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Russell J. T., Thorn N. A. Calcium and stimulus-secretion coupling in the neurohypophysis. II. Effects of lanthanum, a verapamil analogue (D600) and prenylamine on 45-calcium transport and vasopressin release in isolated rat neurohypophyses. Acta Endocrinol (Copenh) 1974 Jul;76(3):471–487. [PubMed] [Google Scholar]
  27. Trifaró J. M. Common mechanisms of hormone secretion. Annu Rev Pharmacol Toxicol. 1977;17:27–47. doi: 10.1146/annurev.pa.17.040177.000331. [DOI] [PubMed] [Google Scholar]
  28. Trifaró J. M., Poisner A. M., Douglas W. W. The fate of the chromaffin granule during catecholamine release from the adrenal medulla. I. Unchanged efflux of phospholipid and cholesterol. Biochem Pharmacol. 1967 Nov;16(11):2095–2100. doi: 10.1016/0006-2952(67)90006-8. [DOI] [PubMed] [Google Scholar]
  29. Zengel J. E., Magleby K. L. Transmitter release during repetitive stimulation: selective changes produced by Sr2+ and Ba2+. Science. 1977 Jul 1;197(4298):67–69. doi: 10.1126/science.17160. [DOI] [PubMed] [Google Scholar]

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