TYROSINE KINASE INHIBITORS ENHANCE CGMP PRODUCTION IN RAT PINEALOCYTES

The role of tyrosine kinase(s) in the regulation of cGMP accumulation in rat pinealocytes was investigated using three tyrosine kinase inhib itors. Treatment with genistein, erbstatin or the active analogues of tyrphostin selectively increased basal cGMP accumulation in a dose-dep endent manner without a concomitant increase in cAMP. In contrast to t he norepinephrine- and vasoactive intestinal peptide-stimulated cGMP r esponses, the stimulatory effect of genistein was not blocked by the n itric oxide synthase inhibitor N-G-monomethyl-L-arginine. Furthermore, in the presence of isobutylmethylxanthine, a phosphodiesterase inhibi tor, neither genistein nor erbstatin had an effect on cGMP accumulatio n. These results indicate that tyrosine kinase inhibitors increase pin eal cGMP accumulation through inhibition of the metabolism of cGMP. (C ) 1995 Academic Press, Inc.