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Br J Pharmacol
2002 Jan 01;1352:313-22. doi: 10.1038/sj.bjp.0704475.
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Functional characterization of an endogenous Xenopus oocyte adenosine receptor.
Kobayashi T
,
Ikeda K
,
Kumanishi T
.
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To investigate the effects of adenosine on endogenous Xenopus oocyte receptors, we analysed defolliculated oocytes injected with mRNAs for the G protein-activated inwardly rectifying K(+) (GIRK) channels. In oocytes injected with mRNAs for either GIRK1/GIRK2 or GIRK1/GIRK4 subunits, application of adenosine or ATP reversibly induced inward K(+) currents, although ATP was less potent than adenosine. The responses were attenuated by caffeine, a non-selective adenosine receptor antagonist. Furthermore, in uninjected oocytes from the same donor, adenosine produced no significant current. The endogenous receptor was activated by two selective A(1) adenosine receptor agonists, N(6)-cyclopentyladenosine (CPA) and N(6)-cyclohexyladenosine (CHA), and antagonized by a selective A(1) adenosine receptor antagonist, 1,3-dipropyl-8-cyclopenylxanthine (DPCPX) at moderate nanomolar concentrations, but insensitive to micromolar concentrations of selective A(2A) and A(3) adenosine receptor agonists, 2-[p-(2-carbonyl-ethyl)-phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680) and N(6)-(3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine (IB-MECA), respectively. However, the pharmacological characteristics of the receptor were different from those of the cloned Xenopus A(1) adenosine receptor and previously proposed adenosine receptors. The adenosine-induced GIRK currents were abolished by injection of pertussis toxin and CPA inhibited forskolin-stimulated cyclic AMP accumulation. We conclude that an adenosine receptor on the Xenopus oocyte membrane can activate GIRK channels and inhibit adenylyl cyclase via G(i/o) proteins. Moreover, our results suggest the existence of an endogenous adenosine receptor with the unique pharmacological characteristics. As the receptor was activated by nanomolar concentrations of adenosine, which is a normal constituent of extracellular fluid, the receptor may be involved in some effects through the G(i/o) protein signalling pathways in ovarian physiology.
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