Correlation between the inhibition of phosphorylation in platelet myosin light chains and the inhibition of platelet aggregation by a new calcium and calmodulin antagonist

The recently synthesized compound 1,2,5-trimethyl-4-phenyl-4-β-(N-methyl-N-4′-methoxybenzyl)-ethylamino]piperidine dihydrochloride (AR-3), which is a derivative of 1,2,5-trimethyl-4-phenyl-4-β-(N,N-disubstituted-ethylamino)]piperidines, was tested for its effects on platelet aggregation and phosphorylation of light myosin chains isolated from platelets. AR-3 caused 50% inhibition of platelet aggregation in concentrations of 25.5 to 32.2 μM (depending on the aggregation inducer used) and 50% inhibition of light myosin chain phosphorylation in a concentration of 70 μM or, when 1 μM calmodulin was added, 120 μM. The good correlation found between the inhibitory effects of AR-3 on platelet aggregation and the phosphorylation of light myosin chains from platelets indicates that this compound inhibits platelet aggregation largely by inhibiting the Ca²⁺-calmodulin-dependent phosphorylation of platelet myosin light chains, acting in this respect similarly to the well-known calmodulin antagonist W-7. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 40–42, July, 1996