IS THE BRADYKININ-INDUCED CA2+ INFLUX AND THE FORMATION OF ENDOTHELIUM-DERIVED RELAXING FACTOR MEDIATED BY A G-PROTEIN

In cultured porcine aortic endothelial cells bradykinin produced a long-lasting Ca2+ influx. In contrast to the G protein-independent Ca2+ entry evoked by ionomycin or digitonin, bradykinin-induced Ca2+ influx was antagonized by Ni2+ with an IC50 value of about 50-mu-M. Since identical IC50 values for Ni2+ were found when Ca2+ entry was induced by sodium fluoride or GTP-gamma-S, we suggest that stimulation of G protein(s) results in the activation of the same Ca2+ channels as stimulation by bradykinin. This conclusion is supported by our findings that inhibition of GTPase by mepacrine amplified bradykinin-stimulated Ca2+ influx, but did not interfere with the effect of the Ca2+ ionophore A23187. Similar to its effect on Ca2+ influx, mepacrine also potentiated endothelium-derived relaxing factor (EDRF) formation by bradykinin and sodium fluoride, but did not affect A23187-induced EDRF biosynthesis. We therefore suggest that in endothelial cells the bradykinin-induced Ca2+ influx and the resulting formation of EDRF are regulated by a G protein.