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 inhibitors. Treatment with genistein, erbstatin or the active analogues of tyrphostin selectively increased basal cGMP accumulation in a dose-dependent manner without a concomitant increase in cAMP. In contrast to the norepinephrine- and vasoactive intestinal peptide-stimulated cGMP responses, the stimulatory effect of genistein was not blocked by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine. Furthermore, in the presence of isobutylmethylxanthine, a phosphodiesterase inhibitor, neither genistein nor erbstatin had an effect on cGMP accumulation. These results indicate that tyrosine kinase inhibitors increase pineal cGMP accumulation through inhibition of the metabolism of cGMP.