[Effects of cordarone on Ca2+-dependent cellular systems].
Cordarone was studied for effects on the pharmacological receptors of myocardial potential-dependent Ca channels, on the receptor-dependent increase in platelet Ca2+ content, on muscarinic cholinergic receptors of the M1- and M2-type, and on calmodulin regulation of cAMP phosphodiesterase (PDE). Without showing selectivity, cordarone is able to interact both with M1-, and M2-muscarinic choline receptors with Ki = 5.3-5.6 microM. Cordarone was found to displace [3H]-nitrendipine with Ki = 1.25 microM and [3H]-desmethoxyverapamil with Ki = 1 microM. The pattern of ligand displacement suggests that the interaction of cordarone with these receptors has no competition. Cordarone was demonstrated to affect neither PDE activity nor its activation with calmodulin. Cordarone suppressed a platelet activation factor-induced increase in intracellular Ca2+ levels in the thrombocytes. Thus, cordarone is capable of affecting Ca2(+)-dependent processes at Ca2+ entry across the potential-dependent Ca channels and influencing the receptor-dependent platelet Ca2+ mobilization and muscarinic cholinergic regulation. The above effects may underlie antiarrhythmic action and determine vascular dilating and anti-fibrillating properties of cordarone.
Kurennaia
G S
GS
Baldenkov
G N
GN
Tkachuk
V A
VA
Mazur
N A
NA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism
D015220:Calcium Channels; D002147:Calmodulin; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000638:Amiodarone; D002118:Calcium
Deĭstvie kordarona na Ca2+-zavisimye sistemy kletki.