Antagonism of an adenosine/ATP receptor in follicular Xenopus oocytes.
Follicular Xenopus oocytes possess a novel receptor where both adenosine and ATP activate a cAMP-dependent, nonrectifying K+-current. Five compounds, alpha,beta-methylene ATP (alpha, beta-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: alpha,beta-meATP (6.72) = 8-SPT (6.68) > theophylline (5.32) > PIT (4.58), whereas suramin was relatively inactive. The blocking actions of alpha,beta-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, alpha,beta-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 in Xenopus oocytes, whereas alpha,beta-meATP and PIT were nonselective in their blocking actions and suramin was relatively inactive.
King
B F
BF
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, England.
Wildman
S S
SS
Townsend-Nicholson
A
A
Burnstock
G
G
D000241:Adenosine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000378:metabolism / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014982:Xenopus laevis
D015221:Potassium Channels; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D005640:Follicle Stimulating Hormone; D013806:Theophylline; D000241:Adenosine