Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1985 Sep;86(1):171–180. doi: 10.1111/j.1476-5381.1985.tb09447.x

The effects of the dihydropyridine Bay K 8644 in guinea-pig isolated trachealis.

S L Allen, R W Foster, R C Small, R Towart
PMCID: PMC1916862  PMID: 2413935

Abstract

In trachea bathed by Krebs solution containing indomethacin 0.8 mumol l-1, Bay K 8644 (0.01-1 mumol l-1) evoked mild spasm. Peak tension was achieved after 10 min and was generally less than 20% of an acetylcholine (ACh) maximum. The effect of Bay K 8644 was not potentiated by addition of 2.5 mmol l-1 potassium chloride (KCl) to the Krebs solution. Bay K 8644 (1 mumol l-1) caused a small potentiation of KCl and tetraethylammonium (TEA). In contrast it did not modify the actions of ACh or histamine. Bay K 8644 (1 mumol l-1) caused a small potentiation of the effect of calcium chloride (CaCl2) tested in trachea bathed by a K+-rich, Ca2+-free, MOPS-buffered physiological salt solution. Organic inhibitors of calcium influx such as nifedipine (0.1 mumol l-1), verapamil (1 mumol l-1) or diltiazem (10 mumol l-1) each caused marked depression of concentration-effect curves to KCl. Bay K 8644 (0.01-1 mumol l-1) provided concentration-dependent protection against this effect in all three cases. Estimation of calcium influx by the lanthanum technique revealed that Bay K 8644 (1 mumol l-1) was able to promote the cellular influx of Ca2+. Intracellular electrophysiological recording showed that Bay K 8644 (1 mumol l-1) caused no change in the resting membrane potential of trachealis cells and no change in the properties of the spontaneous electrical slow waves. However, Bay K 8644 was able to delay the slow wave suppression evoked by 1 mumol l-1 nifedipine. The ability of Bay K 8644 to promote Ca2+ influx and its ability to protect against the effects of several structurally-unrelated inhibitors of Ca2+ influx are consistent with Bay K 8644 acting as an agonist at the dihydropyridine receptor associated with the voltage-operated Ca2+ channel (VOC) of trachealis muscle. By this action it potentiates those spasmogens (KCl, TEA) which act by permitting Ca2+ influx through VOCs. In contrast it has no effect on those spasmogens (ACh, histamine) which principally act to liberate Ca2+ from intracellular sites of sequestration.

Full text

PDF
179

Selected References

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

  1. Ahmed F., Foster R. W., Small R. C. Some effects of nifedipine in guinea-pig isolated trachealis. Br J Pharmacol. 1985 Apr;84(4):861–869. doi: 10.1111/j.1476-5381.1985.tb17380.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dixon J. S., Small R. C. Evidence of poor conduction of muscle excitation in the longitudinal axis of guinea-pig isolated trachea. Br J Pharmacol. 1983 May;79(1):75–83. doi: 10.1111/j.1476-5381.1983.tb10498.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Foster R. W. A correlation between inhibition of the uptake of 3H from (+)-3H-noradrenaline and potentiation of the responses to (-)-noradrenaline in the guinea-pig isolated trachea. Br J Pharmacol Chemother. 1968 Jun;33(2):357–367. doi: 10.1111/j.1476-5381.1968.tb00996.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Foster R. W., Okpalugo B. I., Small R. C. Antagonism of Ca2+ and other actions of verapamil in guinea-pig isolated trachealis. Br J Pharmacol. 1984 Mar;81(3):499–507. doi: 10.1111/j.1476-5381.1984.tb10103.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Foster R. W., Small R. C., Weston A. H. Evidence that the spasmogenic action of tetraethylammonium in guinea-pig trachealis is both direct and dependent on the cellular influx of calcium ion. Br J Pharmacol. 1983 May;79(1):255–263. doi: 10.1111/j.1476-5381.1983.tb10519.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Freedman S. B., Miller R. J. Calcium channel activation: a different type of drug action. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5580–5583. doi: 10.1073/pnas.81.17.5580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gorman A. L., Levy S., Nasi E., Tillotson D. Intracellular calcium measured with calcium-sensitive micro-electrodes and Arsenazo III in voltage-clamped Aplysia neurones. J Physiol. 1984 Aug;353:127–142. doi: 10.1113/jphysiol.1984.sp015327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hess P., Lansman J. B., Tsien R. W. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984 Oct 11;311(5986):538–544. doi: 10.1038/311538a0. [DOI] [PubMed] [Google Scholar]
  9. Jetley M., Weston A. H. Some effects of sodium nitroprusside, methoxyverapamil (D600) and nifedipine on rat portal vein. Br J Pharmacol. 1980 Feb;68(2):311–319. doi: 10.1111/j.1476-5381.1980.tb10420.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kanmura Y., Itoh T., Kuriyama H. Agonist actions of Bay K 8644, a dihydropyridine derivative, on the voltage-dependent calcium influx in smooth muscle cells of the rabbit mesenteric artery. J Pharmacol Exp Ther. 1984 Dec;231(3):717–723. [PubMed] [Google Scholar]
  11. Schramm M., Thomas G., Towart R., Franckowiak G. Activation of calcium channels by novel 1,4-dihydropyridines. A new mechanism for positive inotropics or smooth muscle stimulants. Arzneimittelforschung. 1983;33(9):1268–1272. [PubMed] [Google Scholar]
  12. Schramm M., Thomas G., Towart R., Franckowiak G. Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature. 1983 Jun 9;303(5917):535–537. doi: 10.1038/303535a0. [DOI] [PubMed] [Google Scholar]
  13. Small R. C. Electrical slow waves and tone of guinea-pig isolated trachealis muscle: effects of drugs and temperature changes. Br J Pharmacol. 1982 Sep;77(1):45–54. doi: 10.1111/j.1476-5381.1982.tb09267.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Yamamoto H., Hwang O., Van Breemen C. Bay K8644 differentiates between potential and receptor operated Ca2+ channels. Eur J Pharmacol. 1984 Jul 20;102(3-4):555–557. doi: 10.1016/0014-2999(84)90581-8. [DOI] [PubMed] [Google Scholar]

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

RESOURCES