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 microM. 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.
Graier
W F
WF
Institut für Pharmakodynamik und Toxikologie, Universität, Graz, Austria.
Schmidt
K
K
Kukovetz
W R
WR
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D012969:Sodium Fluoride / Q000494:pharmacology; D013552:Swine
D009569:Nitric Oxide; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000001:Calcimycin; C022838:nickel chloride; D009532:Nickel; D012969:Sodium Fluoride; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D001920:Bradykinin; D002118:Calcium