Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Jul;91(3):569–578. doi: 10.1111/j.1476-5381.1987.tb11250.x

Effect of the K+ efflux stimulating vasodilator BRL 34915 on 86Rb+ efflux and spontaneous activity in guinea-pig portal vein.

U Quast
PMCID: PMC1853539  PMID: 3038244

Abstract

The effect of BRL 34915 on 86Rb+ efflux and myogenic activity was studied simultaneously in guinea-pig portal vein. 86Rb+ was used as a tracer ion for K+. BRL 34915 inhibited myogenic activity with an IC50 value of 12 +/- 2 nM by reducing primarily the frequency of spontaneous contractions. Washout of the substance was followed by hyperreactivity of the vessel. 86Rb+ efflux was slightly reduced by concentrations of BRL 34915 below 100 nM; above 300 nM efflux was increased in a concentration-dependent manner. Above 10 microM BRL 34915, a slow desensitization of the effect on flux was observed during the 10 min application period of the agonist. The Ca2+ entry blocker, isradipine (PN 200-110, 200-500 nM) did not modify BRL 34915-stimulated 86Rb+ efflux at any BRL 34915 concentration tested, indicating that the influx of extracellular Ca2+ through dihydropyridine-sensitive Ca2+ channels is not necessary for this effect. However, by abolishing spontaneous activity, it allowed the 86Rb+ efflux promoting effect of BRL 34915 to be observed at a concentration of 60 nM. The K+ channel blockers tetraethylammonium and 3,4 diaminopyridine inhibited the BRL 34915-induced 86Rb+ efflux with IC50 values of 13 and 3 mM, respectively. Cell permeable derivatives of cyclic AMP and cyclic GMP had no major effect on BRL 34915-induced 86Rb+ flux, indicating that cyclic nucleotide-induced phosphorylation does not play an important modulatory role here. In conclusion, there is an at least 5 fold difference between the concentrations of BRL 34915 necessary to inhibit myogenic activity and those needed to stimulate 86Rb+ efflux. This may be explained by a primary effect of BRL 34915 on the pacemaker cells of the portal vein. explained by a primary effect of BRL 34915 on the pacemaker cells of the portal efflux. This may be

Full text

PDF
569

Selected References

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

  1. Allen S. L., Boyle J. P., Cortijo J., Foster R. W., Morgan G. P., Small R. C. Electrical and mechanical effects of BRL34915 in guinea-pig isolated trachealis. Br J Pharmacol. 1986 Oct;89(2):395–405. doi: 10.1111/j.1476-5381.1986.tb10273.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bolton T. B., Clapp L. H. The diverse effects of noradrenaline and other stimulants on 86Rb and 42K efflux in rabbit and guinea-pig arterial muscle. J Physiol. 1984 Oct;355:43–63. doi: 10.1113/jphysiol.1984.sp015405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bolton T. B., Clark J. P. Actions of various muscarinic agonists on membrane potential, potassium efflux, and contraction of longitudinal muscle of guinea-pig intestine. Br J Pharmacol. 1981 Feb;72(2):319–334. doi: 10.1111/j.1476-5381.1981.tb09131.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DURBIN R. P., JENKINSON D. H. The effect of carbachol on the permeability of depolarized smooth muscle to inorganic ions. J Physiol. 1961 Jun;157:74–89. doi: 10.1113/jphysiol.1961.sp006706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Hof R. P., Hof A., Scholtysik G., Menninger K. Effects of the new calcium antagonist PN 200-110 on the myocardium and the regional peripheral circulation in anesthetized cats and dogs. J Cardiovasc Pharmacol. 1984 May-Jun;6(3):407–416. doi: 10.1097/00005344-198405000-00006. [DOI] [PubMed] [Google Scholar]
  7. Hof R. P., Scholtysik G., Loutzenhiser R., Vuorela H. J., Neumann P. PN 200-110, a new calcium antagonist: electrophysiological, inotropic, and chronotropic effects on guinea pig myocardial tissue and effects on contraction and calcium uptake of rabbit aorta. J Cardiovasc Pharmacol. 1984 May-Jun;6(3):399–406. [PubMed] [Google Scholar]
  8. Imaizumi Y., Watanabe M. The effect of tetraethylammonium chloride on potassium permeability in the smooth muscle cell membrane of canine trachea. J Physiol. 1981 Jul;316:33–46. doi: 10.1113/jphysiol.1981.sp013770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Inoue R., Kitamura K., Kuriyama H. Two Ca-dependent K-channels classified by the application of tetraethylammonium distribute to smooth muscle membranes of the rabbit portal vein. Pflugers Arch. 1985 Oct;405(3):173–179. doi: 10.1007/BF00582557. [DOI] [PubMed] [Google Scholar]
  10. Inoue R., Okabe K., Kitamura K., Kuriyama H. A newly identified Ca2+ dependent K+ channel in the smooth muscle membrane of single cells dispersed from the rabbit portal vein. Pflugers Arch. 1986 Feb;406(2):138–143. doi: 10.1007/BF00586674. [DOI] [PubMed] [Google Scholar]
  11. Levitan I. B. Phosphorylation of ion channels. J Membr Biol. 1985;87(3):177–190. doi: 10.1007/BF01871217. [DOI] [PubMed] [Google Scholar]
  12. Martin W., Gordon J. L. Differential calcium dependence of contractile responses and 86Rb efflux from the rabbit aorta induced by vasoactive stimuli. J Cell Physiol. 1983 Apr;115(1):46–52. doi: 10.1002/jcp.1041150108. [DOI] [PubMed] [Google Scholar]
  13. Schultz K. D., Böhme E., Kreye V. A., Schultz G. Relaxation of hormonally stimulated smooth muscular tissues by the 8-bromo derivative of cyclic GMP. Naunyn Schmiedebergs Arch Pharmacol. 1979 Jan;306(1):1–9. doi: 10.1007/BF00515586. [DOI] [PubMed] [Google Scholar]
  14. Wahlström B. A. Ionic fluxes in the rat portal vein and the applicability of the Goldman equation in predicting the membrane potential from flux data. Acta Physiol Scand. 1973 Nov;89(3):436–448. doi: 10.1111/j.1748-1716.1973.tb05539.x. [DOI] [PubMed] [Google Scholar]
  15. Weir S. W., Weston A. H. Effect of apamin on responses to BRL 34915, nicorandil and other relaxants in the guinea-pig taenia caeci. Br J Pharmacol. 1986 May;88(1):113–120. doi: 10.1111/j.1476-5381.1986.tb09477.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Weir S. W., Weston A. H. The effects of BRL 34915 and nicorandil on electrical and mechanical activity and on 86Rb efflux in rat blood vessels. Br J Pharmacol. 1986 May;88(1):121–128. doi: 10.1111/j.1476-5381.1986.tb09478.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES