Adenosine inhibits a non‐inactivating K+ current in bovine adrenal cortical cells by activation of multiple P1 receptors

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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-β-S for GTP in the pipette, or by replacing ATP with AMP-PNP or UTP. 6 In addition to inhibiting IAC, adenosine (10 μM) 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.

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