GENISTEIN, AN INHIBITOR OF PROTEIN-TYROSINE KINASE, IS ALSO A COMPETITIVE ANTAGONIST FOR P-1-PURINERGIC (ADENOSINE) RECEPTOR IN FRTL-5 THYROID-CELLS

Genistein, a potent inhibitor for protein tyrosine kinase, remarkably inhibited the stimulatory action of N-6-(L-2-phenylisopropyl)adenosine (PIA), an A(1)-adenosine receptor agonist, on thyrotropin (TSH)-induced phospholipase C activation in FRTL-5 thyroid cells. This drug also suppressed both the A(1)-receptor-mediated inhibition of cAMP accumulation in the cells and binding of [H-3]8-cyclopentyl-1,3-dipropylxanthine, a specific antagonist for A(1)-receptor, to the cell membranes in a competitive manner. Adenosine-induced cAMP accumulation through A(2)-receptor in pertussis toxin-treated cells was also competitively antagonized by genistein. We conclude that genistein is also a competitive antagonist for P-1-purinergic receptors. (C) 1994 Academic Press, Inc.