Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptors and cAMP-dependent protein kinase. (2024)

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Proc Natl Acad Sci U S A
v.92(26); 1995 Dec 19
PMC40373

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Proc Natl Acad Sci U S A. 1995 Dec 19; 92(26): 12441–12445.

doi:10.1073/pnas.92.26.12441

Abstract

The mechanism by which the endogenous vasodilator adenosine causes ATP-sensitive potassium (KATP) channels in arterial smooth muscle to open was investigated by the whole-cell patch-clamp technique. Adenosine induced voltage-independent, potassium-selective currents, which were inhibited by glibenclamide, a blocker of KATP currents. Glibenclamide-sensitive currents were also activated by the selective adenosine A2-receptor agonist 2-p-(2-carboxethyl)-phenethylamino-5'-N- ethylcarboxamidoadenosine hydrochloride (CGS-21680), whereas 2-chloro-N6-cyclopentyladenosine (CCPA), a selective adenosine A1-receptor agonist, failed to induce potassium currents. Glibenclamide-sensitive currents induced by adenosine and CGS-21680 were largely reduced by blockers of the cAMP-dependent protein kinase (Rp-cAMP[S], H-89, protein kinase A inhibitor peptide). Therefore, we conclude that adenosine can activate KATP currents in arterial smooth muscle through the following pathway: (i) Adenosine stimulates A2 receptors, which activates adenylyl cyclase; (ii) the resulting increase intracellular cAMP stimulates protein kinase A, which, probably through a phosphorylation step, opens KATP channels.

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Selected References

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Meno JR, Ngai AC, Ibayashi S, Winn HR. Adenosine release and changes in pial arteriolar diameter during transient cerebral ischemia and reperfusion. J Cereb Blood Flow Metab. 1991 Nov;11(6):986–993. [PubMed] [Google Scholar]
Simpson RE, Phillis JW. Adenosine deaminase reduces hypoxic and hypercapnic dilatation of rat pial arterioles: evidence for mediation by adenosine. Brain Res. 1991 Jul 12;553(2):305–308. [PubMed] [Google Scholar]
Park KH, Rubin LE, Gross SS, Levi R. Nitric oxide is a mediator of hypoxic coronary vasodilatation. Relation to adenosine and cyclooxygenase-derived metabolites. Circ Res. 1992 Oct;71(4):992–1001. [PubMed] [Google Scholar]
Gidday JM, Park TS. Adenosine-mediated autoregulation of retinal arteriolar tone in the piglet. Invest Ophthalmol Vis Sci. 1993 Aug;34(9):2713–2719. [PubMed] [Google Scholar]
Sawmiller DR, Linden J, Berne RM. Effects of xanthine amine congener on hypoxic coronary resistance and venous and epicardial adenosine concentrations. Cardiovasc Res. 1994 May;28(5):604–609. [PubMed] [Google Scholar]
von Beckerath N, Cyrys S, Dischner A, Daut J. Hypoxic vasodilatation in isolated, perfused guinea-pig heart: an analysis of the underlying mechanisms. J Physiol. 1991 Oct;442:297–319. [PMC free article] [PubMed] [Google Scholar]
Daut J, Standen NB, Nelson MT. The role of the membrane potential of endothelial and smooth muscle cells in the regulation of coronary blood flow. J Cardiovasc Electrophysiol. 1994 Feb;5(2):154–181. [PubMed] [Google Scholar]
Jackson WF. Arteriolar tone is determined by activity of ATP-sensitive potassium channels. Am J Physiol. 1993 Nov;265(5 Pt 2):H1797–H1803. [PubMed] [Google Scholar]
Quayle JM, Standen NB. KATP channels in vascular smooth muscle. Cardiovasc Res. 1994 Jun;28(6):797–804. [PubMed] [Google Scholar]
Nelson MT, Quayle JM. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol. 1995 Apr;268(4 Pt 1):C799–C822. [PubMed] [Google Scholar]
Dart C, Standen NB. Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery. J Physiol. 1993 Nov;471:767–786. [PMC free article] [PubMed] [Google Scholar]
Quayle JM, Bonev AD, Brayden JE, Nelson MT. 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. [PMC free article] [PubMed] [Google Scholar]
Zhang L, Bonev AD, Mawe GM, Nelson MT. Protein kinase A mediates activation of ATP-sensitive K+ currents by CGRP in gallbladder smooth muscle. Am J Physiol. 1994 Sep;267(3 Pt 1):G494–G499. [PubMed] [Google Scholar]
Tucker AL, Linden J. Cloned receptors and cardiovascular responses to adenosine. Cardiovasc Res. 1993 Jan;27(1):62–67. [PubMed] [Google Scholar]
Kirsch GE, Codina J, Birnbaumer L, Brown AM. 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. [PubMed] [Google Scholar]
Sabouni MH, Cushing DJ, Mustafa SJ. Adenosine receptor-mediated relaxation in coronary artery: evidence for a guanyl nucleotide-binding regulatory protein involvement. J Pharmacol Exp Ther. 1989 Dec;251(3):943–948. [PubMed] [Google Scholar]
Furukawa S, Satoh K, Taira N. Opening of ATP-sensitive K+ channels responsible for adenosine A2 receptor-mediated vasodepression does not involve a pertussis toxin-sensitive G protein. Eur J Pharmacol. 1993 May 19;236(2):255–262. [PubMed] [Google Scholar]
Silver PJ, Walus K, DiSalvo J. Adenosine-mediated relaxation and activation of cyclic AMP-dependent protein kinase in coronary arterial smooth muscle. J Pharmacol Exp Ther. 1984 Feb;228(2):342–347. [PubMed] [Google Scholar]
Collis MG, Brown CM. Adenosine relaxes the aorta by interacting with an A2 receptor and an intracellular site. Eur J Pharmacol. 1983 Dec 9;96(1-2):61–69. [PubMed] [Google Scholar]
Anand-Srivastava MB, Franks DJ. Stimulation of adenylate cyclase by adenosine and other agonists in mesenteric artery smooth muscle cells in culture. Life Sci. 1985 Sep 2;37(9):857–867. [PubMed] [Google Scholar]
Cushing DJ, Brown GL, Sabouni MH, Mustafa SJ. Adenosine receptor-mediated coronary artery relaxation and cyclic nucleotide production. Am J Physiol. 1991 Aug;261(2 Pt 2):H343–H348. [PubMed] [Google Scholar]
Pennanen MF, Bass BL, Dziki AJ, Harmon JW. Adenosine: differential effect on blood flow to subregions of the upper gastrointestinal tract. J Surg Res. 1994 May;56(5):461–465. [PubMed] [Google Scholar]
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. [PubMed] [Google Scholar]
Quayle JM, McCarron JG, Brayden JE, Nelson MT. Inward rectifier K+ currents in smooth muscle cells from rat resistance-sized cerebral arteries. Am J Physiol. 1993 Nov;265(5 Pt 1):C1363–C1370. [PubMed] [Google Scholar]
Ashcroft SJ, Ashcroft FM. Properties and functions of ATP-sensitive K-channels. Cell Signal. 1990;2(3):197–214. [PubMed] [Google Scholar]
Jacobson KA, van Galen PJ, Williams M. Adenosine receptors: pharmacology, structure-activity relationships, and therapeutic potential. J Med Chem. 1992 Feb 7;35(3):407–422. [PMC free article] [PubMed] [Google Scholar]
Feigl EO. Coronary physiology. Physiol Rev. 1983 Jan;63(1):1–205. [PubMed] [Google Scholar]
Cabell F, Weiss DS, Price JM. Inhibition of adenosine-induced coronary vasodilation by block of large-conductance Ca(2+)-activated K+ channels. Am J Physiol. 1994 Oct;267(4 Pt 2):H1455–H1460. [PubMed] [Google Scholar]
Scornik FS, Codina J, Birnbaumer L, Toro L. Modulation of coronary smooth muscle KCa channels by Gs alpha independent of phosphorylation by protein kinase A. Am J Physiol. 1993 Oct;265(4 Pt 2):H1460–H1465. [PubMed] [Google Scholar]
Kume H, Hall IP, Washabau RJ, Takagi K, Kotlikoff MI. Beta-adrenergic agonists regulate KCa channels in airway smooth muscle by cAMP-dependent and -independent mechanisms. J Clin Invest. 1994 Jan;93(1):371–379. [PMC free article] [PubMed] [Google Scholar]
Nelson MT, Patlak JB, Worley JF, Standen NB. Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. Am J Physiol. 1990 Jul;259(1 Pt 1):C3–18. [PubMed] [Google Scholar]
Mills I, Gewirtz H. Cultured vascular smooth muscle cells from porcine coronary artery possess A1 and A2 adenosine receptor activity. Biochem Biophys Res Commun. 1990 May 16;168(3):1297–1302. [PubMed] [Google Scholar]
Abebe W, Makujina SR, Mustafa SJ. Adenosine receptor-mediated relaxation of porcine coronary artery in presence and absence of endothelium. Am J Physiol. 1994 May;266(5 Pt 2):H2018–H2025. [PubMed] [Google Scholar]
Holz FG, Steinhausen M. Renovascular effects of adenosine receptor agonists. Ren Physiol. 1987;10(5):272–282. [PubMed] [Google Scholar]
Edvinsson L, Fredholm BB. Characterization of adenosine receptors in isolated cerebral arteries of cat. Br J Pharmacol. 1983 Dec;80(4):631–637. [PMC free article] [PubMed] [Google Scholar]
Merkel LA, Lappe RW, Rivera LM, Cox BF, Perrone MH. 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]
Nelson MT, Huang Y, Brayden JE, Hescheler J, Standen NB. Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels. Nature. 1990 Apr 19;344(6268):770–773. [PubMed] [Google Scholar]
Standen NB, Quayle JM, Davies NW, Brayden JE, Huang Y, Nelson MT. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science. 1989 Jul 14;245(4914):177–180. [PubMed] [Google Scholar]
Jackson WF, König A, Dambacher T, Busse R. Prostacyclin-induced vasodilation in rabbit heart is mediated by ATP-sensitive potassium channels. Am J Physiol. 1993 Jan;264(1 Pt 2):H238–H243. [PubMed] [Google Scholar]
Kitazono T, Faraci FM, Heistad DD. Effect of norepinephrine on rat basilar artery in vivo. Am J Physiol. 1993 Jan;264(1 Pt 2):H178–H182. [PubMed] [Google Scholar]
Narishige T, Egashira K, Akatsuka Y, Imamura Y, Takahashi T, Kasuya H, Takesh*ta A. Glibenclamide prevents coronary vasodilation induced by beta 1-adrenoceptor stimulation in dogs. Am J Physiol. 1994 Jan;266(1 Pt 2):H84–H92. [PubMed] [Google Scholar]
Edwards RM, Stack EJ, Trizna W. Calcitonin gene-related peptide stimulates adenylate cyclase and relaxes intracerebral arterioles. J Pharmacol Exp Ther. 1991 Jun;257(3):1020–1024. [PubMed] [Google Scholar]
Gu ZF, Jensen RT, Maton PN. A primary role for protein kinase A in smooth muscle relaxation induced by adrenergic agonists and neuropeptides. Am J Physiol. 1992 Sep;263(3 Pt 1):G360–G364. [PubMed] [Google Scholar]
Parfenova H, Hsu P, Leffler CW. Dilator prostanoid-induced cyclic AMP formation and release by cerebral microvascular smooth muscle cells: inhibition by indomethacin. J Pharmacol Exp Ther. 1995 Jan;272(1):44–52. [PubMed] [Google Scholar]

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Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptors and cAMP-dependent protein kinase. (2024)

FAQs

What is the mechanism of action of adenosine potassium channel? ›

Therefore, we conclude that adenosine can activate KATP currents in arterial smooth muscle through the following pathway: (i) Adenosine stimulates A2 receptors, which activates adenylyl cyclase; (ii) the resulting increase intracellular cAMP stimulates protein kinase A, which, probably through a phosphorylation step, ...

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What is the function of the ATP-sensitive potassium channel? ›

ATP-sensitive potassium (K_ATP) channels, so named because they are inhibited by intracellular _ATP, play key physiological roles in many tissues. In pancreatic β cells, these channels regulate glucose-dependent insulin secretion and serve as the target for sulfonylurea drugs used to treat type 2 diabetes.

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Which channel does adenosine block? ›

Adenosine inhibits calcium channel currents via A1 receptors on salamander retinal ganglion cells in a mini-slice preparation. J Neurochem. 2002 May;81(3):550-6. doi: 10.1046/j.

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What do ATP dependent K channels do? ›

In the pancreatic β-cell, ATP-sensitive potassium (K_ATP) channels link glucose metabolism and insulin secretion and are essential to the normal regulation of plasma glucose and other nutrients [1,2]. At low glucose, intracellular [ATP]/[ADP] is low, and K_ATP channels are open, hyperpolarizing the cell membrane.

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What is the mechanism of action of adenosine cAMP? ›

Increased concentrations of adenosine activate adenosine receptors coupled to Gs or Gi proteins, which in turn regulates the activity of adenylyl cyclases leading to an increase or decrease in cAMP concentrations and stimulation of downstream effectors.

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What is the mechanism of action of adenosine quizlet? ›

Adenosine slow supraventricular tachycardia by decreasing electrical conduction through the AV node without causing negative inotropic effects. It acts directly on the sinus pacemaker cells and vagal nerve terminals to decrease chronotropic (heart rate) activity.

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How do you block adenosine receptors? ›

Methylxanthines – such as caffeine, theophylline, and theobromine – are naturally occurring substances found in coffee, tea, and chocolate that block adenosine receptors. Caffeine binds to adenosine receptors in the brain and blocks them, preventing adenosine from activating them [83, 84].

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What drug blocks adenosine receptors? ›

Istradefylline selectively binds to and inhibits adenosine A2A receptors. These receptors are G-protein-coupled receptors present in the basal ganglia, a part of the brain that controls movements.

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What blocks adenosine receptors in the brain _____? ›

Caffeine is a potent adenosine receptor antagonist with roughly equally high affinity for both A₁ and A_2A receptors. Work in mice provided strong evidence that caffeine promotes wakefulness primarily by blocking the A_2A subtype of adenosine receptors (Huang et al., ²⁰⁰⁵).

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What are adenosine triphosphate ATP-sensitive potassium channels? ›

ATP-sensitive potassium channels (K_ATP) are widely distributed and present in a number of tissues including muscle, pancreatic beta cells and the brain. Their activity is regulated by adenine nucleotides, characteristically being activated by falling ATP and rising ADP levels.

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What is ATP-sensitive potassium channel opener? ›

ATP-sensitive potassium channels are regulated by the ATP/ADP ratio in a way that a drop of this ratio will activate these channels. Following their opening, the efflux of potassium will induce a hyperpolarization, decreasing the neuronal excitability.

Why does ATP close potassium channels? ›

In the presence of higher glucose metabolism, and consequently increased relative levels of ATP, the K_ATP channels close, causing the membrane potential of the cell to depolarize, activating voltage-gated calcium channels, and thus promoting the calcium-dependent release of insulin.