A POSSIBLE ROLE OF TYROSINE KINASES IN THE REGULATION OF MUSCARINIC RECEPTOR-ACTIVATED CATION CHANNELS IN GUINEA-PIG ILEUM

We investigated the effects of inhibitors for tyrosine kinases and phosphatases on the muscarinic receptor-activated nonselective cationic current. With nystatin-perforated whole-cell recording, the tyrosine kinase inhibitor genistein (1 similar to 10 mu g/ml) reduced the amplitude of currents evoked by iontophoretically applied acetylcholine in a dose-dependent manner, the maximum inhibition being to about 46% of the control. In contrast, daidzein (10 mu g/ml), an inactive analog of genistein, exerted little effect. These effects were unchanged when the cationic current was activated by internal perfusion of GTP gamma S (50 mu M) bypassing the muscarinic receptor. A potent phosphatase inhibitor, orthovanadate (30 similar to 100 mu M), on the other hand, increased the GTP gamma S-induced cationic current. These results suggest that tyrosine phosphorylation may be essential to regulate the Ca mobilization associated with muscarinic receptor-operated nonselective cation channels. (C) 1994 Academic Inc. Press,