Molecular mechanisms of vasoconstrictor action of imidazo[1,2-alpha]benzimidazole derivative RU-1117 possessing local anesthetic properties.
We studied the mechanisms of action of imidazobenzimidazole derivative RU-1117 on calcium homeostasis in myocytes isolated from rat thoracic aorta. In therapeutic concentrations, RU-1117 increased the content of free calcium ions due to their mobilization from intracellular depot via the IP3-dependent mechanisms. Antagonists of angiotensin II AT1-receptors irbesartan and, to greater extent, eprosartan abolished the calcium-mobilizing action of RU-1117. Selective antagonist of endothelin ETA-receptors sitaxsentan and alpha1-adrenoceptor agonist prazosin produced no effect on calcium mobilization caused by novel local anesthetic RU-1117.
Galenko-Yaroshevskii
A P
AP
Krasnodar Research Center, Russian Academy of Medical Sciences and Administration of Krasnodar Krai, Moscow, Russia.
Dukhanin
A S
AS
Takhchidi
Kh P
KhP
Malyugin
B E
BE
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000779:Anesthetics, Local; D001562:Benzimidazoles; C492532:RU-1117; D014662:Vasoconstrictor Agents; D002118:Calcium