Influence of mibefradil on Ca2+ influx induced by vasoactive hormones or depletion of intracellular calcium stores.
The influence of the new calcium antagonist mibefradil (CAS 116666-63-8, Ro 405967) on calcium influx into rabbit smooth muscle cells (VSMC) was studied. Angiotensin II-stimulated divalent cations entry was blocked by mibefradil at micromolar concentrations (1-10 mumol/l). In the same range of concentrations, the antagonist depressed capacitative calcium influx evoked by thapsigargin- and 2,5-di-tert-butylhydroquinone (BHQ)-dependent depletion of internal depots. The ability to block the receptor-mediated pathway of calcium current into VSMC may explain in part the difference between the mode of pharmacological action of mibefradil as compared to other calcium antagonists.
Cheglakov
I B
IB
Laboratory of Molecular Endocrinology, Institute of Experimental Cardiology, Moscow, Russia.
Bochkov
V N
VN
Tkachuk
V A
VA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006873:Hydroquinones / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D020748:Mibefradil; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D006873:Hydroquinones; D013764:Tetrahydronaphthalenes; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C019359:2,5-di-tert-butylhydroquinone; D020748:Mibefradil; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2