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Adenosine inhibits a non‐inactivating K + current in bovine adrenal cortical cells by activation of multiple P 1 receptors
Author(s) -
Xu Lin,
Enyeart John J.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.00081.x
Subject(s) - adenosine , cgs 21680 , agonist , receptor , adenosine a1 receptor , chemistry , adenosine receptor , medicine , adenosine a2b receptor , endocrinology , ic50 , patch clamp , microbiology and biotechnology , pharmacology , biochemistry , biology , in vitro
1 Bovine adrenal zona fasciculata (AZF) cells express a non‐inactivating K + current ( I AC ) 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 I AC by a maximum of 78·4 ± 4·6% ( n = 8 ) with an IC 50 of 71 nM. The non‐selective adenosine receptor agonist NECA effectively inhibited I AC by 79·3 ± 2·9% ( n = 24 ) at a concentration of 100 nM. 2 Inhibition of I AC was mediated through multiple P 1 adenosine receptor subtypes. The A 1 ‐selective agonist CCPA (10 nM), the A 2A ‐selective agonist CGS 21680 (100 nM) and the A 3 ‐selective agonist IB‐MECA (10 nM) inhibited I AC by 64·8 ± 8·4, 78·4 ± 4·6 and 69·3 ± 6·9%, respectively. 3 Specific adenosine receptor subtype antagonists including DPCPX (A 1 ), ZM 241385 (A 2A ) and MRS 1191 (A 3 ) effectively blocked inhibition of I AC by adenosine receptor‐selective agonists. 4 A mixture of the three adenosine receptor antagonists completely suppressed inhibition of I AC by adenosine, but failed to alter inhibition by external ATP which acts through a separate P 2 nucleotide receptor. 5 Inhibition of I AC 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 I AC , 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 (A 1 , A 2A , A 3 ), each of which is coupled to the inhibition of I AC K + channels through a G‐protein‐dependent mechanism requiring ATP hydrolysis. Adenosine‐mediated inhibition of I AC is associated with membrane depolarization. Adenosine and other purines may co‐ordinate the stress‐induced secretion of corticosteroids and catecholamines from the adrenal gland.