title: Adenosine inhibits a non-inactivating K+ current in bovine adrenal cortical cells by activation of multiple P1 receptors.
abstract: 1. Bovine adrenal zona fasciculata (AZF) cells express a non-inactivating K+ current (IAC) that sets the resting potential while it is activated by intracellular ATP. In whole-cell patch clamp recordings from bovine AZF cells, we found that adenosine selectively inhibited IAC by a maximum of 78.4 +/- 4.6 % (n = 8) with an IC50 of 71 nM. The non-selective adenosine receptor agonist NECA effectively inhibited IAC by 79.3 +/- 2.9 % (n = 24) at a concentration of 100 nM. 2. Inhibition of IAC was mediated through multiple P1 adenosine receptor subtypes. The A1-selective agonist CCPA (10 nM), the A2A-selective agonist CGS 21680 (100 nM) and the A3-selective agonist IB-MECA (10 nM) inhibited IAC by 64.8 +/- 8.4, 78.4 +/- 4.6 and 69.3 +/- 6.9 %, respectively. 3. Specific adenosine receptor subtype antagonists including DPCPX (A1), ZM 241385 (A2A) and MRS 1191 (A3) effectively blocked inhibition of IAC by adenosine receptor-selective agonists. 4. A mixture of the three adenosine receptor antagonists completely suppressed inhibition of IAC by adenosine, but failed to alter inhibition by external ATP which acts through a separate P2 nucleotide receptor. 5. Inhibition of IAC by adenosine or NECA was eliminated by substituting GDP-beta-S for GTP in the pipette, or by replacing ATP with AMP-PNP or UTP. 6. In addition to inhibiting IAC, adenosine (10 microM) depolarized AZF cells by 46.2 +/- 5.8 mV (n = 6). 7. These results show that bovine AZF cells express at least three adenosine receptor subtypes (A1, A2A, A3), each of which is coupled to the inhibition of IAC K+ channels through a G-protein-dependent mechanism requiring ATP hydrolysis. Adenosine-mediated inhibition of IAC is associated with membrane depolarization. Adenosine and other purines may co-ordinate the stress-induced secretion of corticosteroids and catecholamines from the adrenal gland.
authors.affiliation: Department of Pharmacology, The Ohio State University, College of Medicine, Columbus, OH 43210-1239, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.forename: J J
authors.initials: JJ
authors.lastname: Enyeart
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000145:classification / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; D019830:Adenosine-5'-(N-ethylcarboxamide); D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019204:GTP-Binding Proteins; D000241:Adenosine; D011188:Potassium