[Interaction of calcium agonists and antagonists with Ca-binding proteins and their effect on cyclic nucleotide phosphodiesterase].
The effects of Ca2+ antagonists (nicardipine, felodipine, nitrenedipine, isradipine, niphedipine, darodipine and riodipine) and Ca2+ agonists (BAY K8644 and CGP 28392), 1.4-dihydropyridine derivatives (1.2-DHP), on the calmodulin (CM)-dependent activation of cyclic nuxleotide phosphodiesterase (PDE) were studied. Both the blockers and activators of slow potential-dependent Ca2+ channels induced a un-competitive inhibition of the CM-dependent PDE activity. 1.4-DHP was found to replace the fluorescent probe, diS-C3-(5), from the Ca2(+)-dependent calmodulin-dye complex (K0.5 = 4-60 microM) but at concentrations below 100 microM had no effect on the Ca2(+)-dependent troponin C-dye complex. Darodipine (100 microM) did not interact with the proteins. The 1.4-DHP interaction with CM did not interfere with PDE activation. It is concluded that 1.4-DHP may affect Ca2+ dependent processes not only at the levels of activation or blocking of Ca2+ channels, but also through regulation of Ca2(+)-CM dependent enzymes.
Feoktistov
I A
IA
Baldenkov
G N
GN
Barannik
I V
IV
Cherviakov
E B
EB
Larionov
N P
NP
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002120:Calcium Channel Agonists / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D002417:Cattle; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007700:Kinetics; D011817:Rabbits; D014336:Troponin / Q000378:metabolism
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D014336:Troponin; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases
Vzaimodeĭstvie kal'tsievykh agonistov i antagonistov c Ca-sviazyvaiushchimi belkami i ikh vliianie na fosfodiésterazu tsiklicheskikh nukleotidov.