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Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptors and cAMP-dependent protein kinase.
Kleppisch T, Nelson MT
Proceedings of the National Academy of Sciences USA. 1995;92( 26):12441-5.
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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.
Keyword(s)
Animals; Cells, Cultured; Male; Patch-Clamp Techniques; Rabbits; Sulfonamides; agonists: Receptors, Purinergic P1; analogs & derivatives: Adenosine; analogs & derivatives: Cyclic AMP; antagonists & inhibitors: Cyclic AMP-Dependent Protein Kinases; drug effects: Membrane Potentials; drug effects: Muscle, Smooth, Vascular; drug effects: Potassium Channels; pharmacology: Adenosine Triphosphate; pharmacology: Enzyme Inhibitors; pharmacology: Glyburide; pharmacology: Isoquinolines; pharmacology: Phenethylamines; pharmacology: Thionucleotides; physiology: Mesenteric Arteries