Влияние амитриптилина, имипрамина и хлорпромазина на активность фосфогидролаз

Abstract

We have studied the effects of amitriptyline, imipramine, and neuroleptic chloropromazine on the function of enzyme Ca2+-activating-Mg2+-dependent ATPase of sarcoplasmic reticulum (SPR), Na+, K+-dependent ATPase of endoplasmatic reticulum (EPR), and phosphodiesterase of cyclic adenosine monophosphate (cAMP). It is shown that violation of the enzyme function (decrease of [Ca2+]/[ATP] ratio) or inhibition of the active transport of Ca2+ ions by psychotropic drugs leads to impairment of the Ca transport into SPR vesicle, and to gteh corresponding increase in muscle contraction. This effect decreases with increasing concentrations of amitriptyline and imipramine, and with decreasing concentration of chloropromazine, which is evidence of the different mechanisms of action on Ca2+, Mg2+-ATPase of SPR. Amitriptyline was a noncompetitive reversible inhibitor of Ca2+, Mg2+-ATPase of SPR with a constant of ATP hydrolysis inhibition Ki = 1.8 × 10-4 M, and the constant of active calcium transport inhibition Ki = 0.7 × 10-4 M.