ML-7 AND W-7 FACILITATE THROMBOXANE A(2)-MEDIATED CA2+ MOBILIZATION IN RABBIT PLATELETS

The effects of naphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML- 7), a myosin light chain kinase inhibitor, and N-(6-aminohexyl)-5-chlo ro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, on thrombo xane A(2) receptor-mediated signal transduction were examined in rabbi t washed platelets. ML-7 and W-7 at 10-30 mu M slightly potentiated th e aggregation induced by a thromboxane A(2) receptor agonist, 9,11-did eoxy-9 alpha,11 alpha-epoxymethanoprostaglandin F-2 alpha (U46619), in spite of their known inhibitory actions. ML-7 and W-7 concentration-d ependently enhanced U46619-induced phosphoinositide hydrolysis and the increase in internal free Ca2+ concentration in the presence or absen ce of external Ca2+. While ML-7 and W-7 inhibited basal GTPase activit y, they augmented U46619-induced activation of GTPase in a concentrati on-dependent manner. The present results suggest that ML-7 and W-7 enh ance thromboxane A(2) receptor-mediated signal transduction at the rec eptor/G protein coupling, leading to the enhancement of phosphoinositi de hydrolysis and Ca2+ mobilization, independently of the inhibition o f myosin light chain kinase or calmodulin.