Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Jun;115(4):607–612. doi: 10.1111/j.1476-5381.1995.tb14975.x

The involvement of ATP-sensitive potassium channels in beta-adrenoceptor-mediated vasorelaxation in the rat isolated mesenteric arterial bed.

M D Randall 1, A I McCulloch 1
PMCID: PMC1908500  PMID: 7582479

Abstract

1. We have used the isolated buffer-perfused superior mesenteric arterial bed of the rat to assess the involvement of ATP-sensitive potassium (KATP) channels in the vasorelaxant responses to beta-adrenoceptor agonists. 2. The vasorelaxant potencies of the non-selective beta-adrenoceptor agonist, isoprenaline, the beta 1-adrenoceptor agonist, dobutamine and the beta 2-adrenoceptor agonist, terbutaline were all significantly (P < 0.05) reduced (isoprenaline, ED50 = 265 +/- 31 pmol v. 1.05 +/- 0.42 nmol; dobutamine, ED50 = 294 +/- 67 pmol v. 497 +/- 115 pmol; terbutaline, ED50 = 157 +/- 26 nmol v. 452 +/- 120 nmol) in the presence of the KATP-channel blocker, glibenclamide. 3. The presence of glibenclamide only weakly influenced the vasorelaxant properties of salbutamol, a beta 2-adrenoceptor agonist, while those of verapamil, a beta-adrenoceptor-independent vasorelaxant, were unaffected. 4. In radioligand binding experiments, glibenclamide (1 nM-100 microM) did not displace any specific [3H]-dihydroalprenolol binding from rat beta-adrenoceptors. Therefore, glibenclamide does not bind to beta-adrenoceptors at the concentration used in the present investigation. 5. Vasorelaxant responses to dibutyryl cyclic AMP, the cell permeable analogue of cyclic AMP, were also unaffected by glibenclamide, indicating that the coupling of beta-adrenoceptors to KATP-channels occurs independently of the elevation of intracellular cyclic AMP. 6. We have shown that a significant element of the vasorelaxant responses to both beta 1- and beta 2-adrenoceptor activation involves the opening of KATP-channels. In conclusion, KATP-channels may play a physiological role in beta-adrenoceptor-mediated vasodilatation.

Full text

PDF
610

Selected References

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

  1. Bouchard J. F., Dumont E., Lamontagne D. Evidence that prostaglandins I2, E2, and D2 may activate ATP sensitive potassium channels in the isolated rat heart. Cardiovasc Res. 1994 Jun;28(6):901–905. doi: 10.1093/cvr/28.6.901. [DOI] [PubMed] [Google Scholar]
  2. Brown A. M., Birnbaumer L. Direct G protein gating of ion channels. Am J Physiol. 1988 Mar;254(3 Pt 2):H401–H410. doi: 10.1152/ajpheart.1988.254.3.H401. [DOI] [PubMed] [Google Scholar]
  3. Chamienia A. L., Johns E. J. The renal functional responses to 5-HT1A receptor agonist, flesinoxan, in anaesthetized, normotensive rat. Br J Pharmacol. 1994 May;112(1):214–218. doi: 10.1111/j.1476-5381.1994.tb13054.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cherksey B., Altszuler N. Tolbutamide and glyburide differ in effectiveness to displace alpha- and beta-adrenergic radioligands in pancreatic islet cells and membranes. Diabetes. 1984 May;33(5):499–503. doi: 10.2337/diab.33.5.499. [DOI] [PubMed] [Google Scholar]
  5. Chiu P., Cook S. J., Small R. C., Berry J. L., Carpenter J. R., Downing S. J., Foster R. W., Miller A. J., Small A. M. Beta-adrenoceptor subtypes and the opening of plasmalemmal K(+)-channels in bovine trachealis muscle: studies of mechanical activity and ion fluxes. Br J Pharmacol. 1993 Aug;109(4):1149–1156. doi: 10.1111/j.1476-5381.1993.tb13742.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cook S. J., Small R. C., Berry J. L., Chiu P., Downing S. J., Foster R. W. Beta-adrenoceptor subtypes and the opening of plasmalemmal K(+)-channels in trachealis muscle: electrophysiological and mechanical studies in guinea-pig tissue. Br J Pharmacol. 1993 Aug;109(4):1140–1148. doi: 10.1111/j.1476-5381.1993.tb13741.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dart C., Standen N. B. Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery. J Physiol. 1993 Nov;471:767–786. doi: 10.1113/jphysiol.1993.sp019927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Downing S. J., Hollingsworth M. One way cross tolerance between cromakalim and salbutamol in the uterus of the rat in vivo. Br J Pharmacol. 1992 Jan;105(1):129–134. doi: 10.1111/j.1476-5381.1992.tb14223.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Edwards G., Weston A. H. Potassium channel openers and vascular smooth muscle relaxation. Pharmacol Ther. 1990;48(2):237–258. doi: 10.1016/0163-7258(90)90082-d. [DOI] [PubMed] [Google Scholar]
  10. Jackson W. F. Arteriolar tone is determined by activity of ATP-sensitive potassium channels. Am J Physiol. 1993 Nov;265(5 Pt 2):H1797–H1803. doi: 10.1152/ajpheart.1993.265.5.H1797. [DOI] [PubMed] [Google Scholar]
  11. Kirsch G. E., Codina J., Birnbaumer L., Brown A. M. Coupling of ATP-sensitive K+ channels to A1 receptors by G proteins in rat ventricular myocytes. Am J Physiol. 1990 Sep;259(3 Pt 2):H820–H826. doi: 10.1152/ajpheart.1990.259.3.H820. [DOI] [PubMed] [Google Scholar]
  12. Kitazono T., Faraci F. M., Heistad D. D. Effect of norepinephrine on rat basilar artery in vivo. Am J Physiol. 1993 Jan;264(1 Pt 2):H178–H182. doi: 10.1152/ajpheart.1993.264.1.H178. [DOI] [PubMed] [Google Scholar]
  13. Kroeger E. A., Marshall J. M. Beta-adrenergic effects on rat myometrium: mechanisms of membrane hyperpolarization. Am J Physiol. 1973 Dec;225(6):1339–1345. doi: 10.1152/ajplegacy.1973.225.6.1339. [DOI] [PubMed] [Google Scholar]
  14. Merkel L. A., Lappe R. W., Rivera L. M., Cox B. F., Perrone M. H. Demonstration of vasorelaxant activity with an A1-selective adenosine agonist in porcine coronary artery: involvement of potassium channels. J Pharmacol Exp Ther. 1992 Feb;260(2):437–443. [PubMed] [Google Scholar]
  15. Miura M., Belvisi M. G., Stretton C. D., Yacoub M. H., Barnes P. J. Role of potassium channels in bronchodilator responses in human airways. Am Rev Respir Dis. 1992 Jul;146(1):132–136. doi: 10.1164/ajrccm/146.1.132. [DOI] [PubMed] [Google Scholar]
  16. Nakashima M., Vanhoutte P. M. Isoproterenol causes hyperpolarization through opening of ATP-sensitive potassium channels in vascular smooth muscle of the canine saphenous vein. J Pharmacol Exp Ther. 1995 Jan;272(1):379–384. [PubMed] [Google Scholar]
  17. Narishige T., Egashira K., Akatsuka Y., Imamura Y., Takahashi T., Kasuya H., Takeshita A. Glibenclamide prevents coronary vasodilation induced by beta 1-adrenoceptor stimulation in dogs. Am J Physiol. 1994 Jan;266(1 Pt 2):H84–H92. doi: 10.1152/ajpheart.1994.266.1.H84. [DOI] [PubMed] [Google Scholar]
  18. Nelson M. T., Huang Y., Brayden J. E., Hescheler J., Standen N. B. Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels. Nature. 1990 Apr 19;344(6268):770–773. doi: 10.1038/344770a0. [DOI] [PubMed] [Google Scholar]
  19. Nichols C. G., Lederer W. J. Adenosine triphosphate-sensitive potassium channels in the cardiovascular system. Am J Physiol. 1991 Dec;261(6 Pt 2):H1675–H1686. doi: 10.1152/ajpheart.1991.261.6.H1675. [DOI] [PubMed] [Google Scholar]
  20. Quayle J. M., Bonev A. D., Brayden J. E., Nelson M. T. Calcitonin gene-related peptide activated ATP-sensitive K+ currents in rabbit arterial smooth muscle via protein kinase A. J Physiol. 1994 Feb 15;475(1):9–13. doi: 10.1113/jphysiol.1994.sp020045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Randall M. D., Griffith T. M. Modulation of vasodilatation to levcromakalim by hypoxia and EDRF in the rabbit isolated ear: a comparison with pinacidil, sodium nitroprusside and verapamil. Br J Pharmacol. 1993 Jun;109(2):386–393. doi: 10.1111/j.1476-5381.1993.tb13581.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Randall M. D., Hiley C. R. Effect of phenobarbitone pretreatment upon endothelium-dependent relaxation to acetylcholine in rat superior mesenteric arterial bed. Br J Pharmacol. 1988 Jul;94(3):977–983. doi: 10.1111/j.1476-5381.1988.tb11612.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ribalet B., Ciani S., Eddlestone G. T. ATP mediates both activation and inhibition of K(ATP) channel activity via cAMP-dependent protein kinase in insulin-secreting cell lines. J Gen Physiol. 1989 Oct;94(4):693–717. doi: 10.1085/jgp.94.4.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schackow T. E., Ten Eick R. E. Enhancement of ATP-sensitive potassium current in cat ventricular myocytes by beta-adrenoreceptor stimulation. J Physiol. 1994 Jan 1;474(1):131–145. doi: 10.1113/jphysiol.1994.sp020008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Standen N. B., Quayle J. M., Davies N. W., Brayden J. E., Huang Y., Nelson M. T. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science. 1989 Jul 14;245(4914):177–180. doi: 10.1126/science.2501869. [DOI] [PubMed] [Google Scholar]
  26. Sturgess N. C., Ashford M. L., Cook D. L., Hales C. N. The sulphonylurea receptor may be an ATP-sensitive potassium channel. Lancet. 1985 Aug 31;2(8453):474–475. doi: 10.1016/s0140-6736(85)90403-9. [DOI] [PubMed] [Google Scholar]
  27. Terzic A., Tung R. T., Inanobe A., Katada T., Kurachi Y. G proteins activate ATP-sensitive K+ channels by antagonizing ATP-dependent gating. Neuron. 1994 Apr;12(4):885–893. doi: 10.1016/0896-6273(94)90340-9. [DOI] [PubMed] [Google Scholar]
  28. Torphy T. J. Beta-adrenoceptors, cAMP and airway smooth muscle relaxation: challenges to the dogma. Trends Pharmacol Sci. 1994 Oct;15(10):370–374. doi: 10.1016/0165-6147(94)90157-0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES