RT Journal Article SR Electronic T1 Antagonism of an Adenosine/ATP Receptor in FollicularXenopus Oocytes JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1005 OP 1011 VO 285 IS 3 A1 B. F. King A1 S. S. Wildman A1 A. Townsend-Nicholson A1 G. Burnstock YR 1998 UL http://jpet.aspetjournals.org/content/285/3/1005.abstract AB Follicular Xenopus oocytes possess a novel receptor where both adenosine and ATP activate a cAMP-dependent, nonrectifying K+-current. Five compounds, α,β-methylene ATP (α,β-meATP), 8-(p-sulfophenyl)theophylline (8-SPT), theophylline, 2,2′-pyridylisatogen tosylate (PIT) and suramin, were tested as antagonists of adenosine- and ATP-activated K+-currents. The descending order of activity (pIC50 values) against adenosine responses was: α,β-meATP (6.72) = 8-SPT (6.68) > theophylline (5.32) > PIT (4.58), whereas suramin was relatively inactive. The blocking actions of α,β-meATP and alkylxanthine compounds were reversible with washout, whereas blockade by PIT was irreversible. These antagonists showed similar blocking activity against ATP responses, except for PIT which was more effective at ATP responses than at adenosine responses. The selectivity of antagonists was tested against cAMP-dependent K+-currents evoked by forskolin and follicle-stimulating hormone (FSH). 8-SPT and theophylline did not inhibit but instead augmented forskolin and FSH responses; this augmentation may be caused by inhibition of phosphodiesterase activity inside follicle cells. On the other hand, α,β-MeATP and PIT inhibited forskolin and FSH responses; both compounds apparently are nonselective antagonists. Thus, only alkylxanthine derivatives (8-SPT and theophylline) were selective antagonists of the novel adenosine/ATP receptor inXenopus oocytes, whereas α,β-meATP and PIT were nonselective in their blocking actions and suramin was relatively inactive. The American Society for Pharmacology and Experimental Therapeutics