Modulation by mibefradil of the histamine-induced Ca2+ entry in human aortic endothelial cells.
The effect of mibefradil, known as a T- and L-type Ca(2+) channel antagonist, on the histamine-induced Cl(-) current and Ca(2+) entry was investigated in human aortic endothelial cells by the fluorescence measurement of intracellular Ca(2+) concentration ([Ca(2+)](i)) combined with the patch clamp method. Mibefradil (10 micro M) inhibited both the Cl(-) current and Ca(2+) entry in a concentration-dependent manner with an IC(50) value of 4.8 and 2.6 micro M for the Cl(-) current and [Ca(2+)](i), respectively. These values were comparable to those reported for the inhibition of the T-type Ca(2+) channel and other Cl(-) channels. The suppression of Ca(2+) entry is not caused by the inhibition of the Cl(-) current and the resulting depolarization since the inhibition was still observed under the voltage clamp condition. These results suggest that mibefradil is a potent blocker not only for the agonist-induced Cl(-) current but also Ca(2+) entry channels in vascular endothelial cells.
Yazawa
Kazuto
K
Department of Pharmacology, Akita University School of Medicine, Akita, Japan.
Ono
Kyoichi
K
Iijima
Toshihiko
T
D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology*; D006801:Humans; D020748:Mibefradil / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D013997:Time Factors
D002121:Calcium Channel Blockers; D018118:Chloride Channels; D017442:Histamine Agonists; D020748:Mibefradil; D006632:Histamine; D002118:Calcium