Comparison of the calmodulin antagonists compound 48/80 and calmidazolium

Abstract

The 2 presumed calmodulin antagonists, calmidazolium and compound 48/80, were compared for their effects on several calmodulin-dependent and calmodulin-independent enzyme systems. Compound 48/80 and calmidazolium were about equipotent in antagonizing the calmodulin-dependent fraction of brain phosphodiesterase and erythrocyte Ca2+-transporting ATPase. Compound 48/80 combines high potency with high specificity. The basal, calmodulin-independent activity of calmodulin-regulated enzymes was not suppressed. Calmodulin-independent enzyme activities, such as Ca2+-transporting ATPase of sarcoplasmic reticulum, Mg2+-dependent ATPases of different tissues and Na+/K+-transporting ATPase of cardiac sarcolemma, were far less altered or not altered at all, by compound 48/80 as compared with calmidazolium. Antagonism of proteolysis-induced stimulation as opposed to calmodulin-induced activation of erythrocyte Ca2+-transporting ATPase required a 32 times higher concentration of compound 48/80. Compound 48/80 was a superior antagonist to calmidazolium since inhibition of calmodulin-independent events by the other agent occurred at considerably lower concentrations. Compound 48/80 is apparently a much more specific and useful tool for studing the participation of calmodulin in biological processes than the presently used agents.