PHENCYCLIDINE BLOCK OF CA2-HEART SARCOPLASMIC-RETICULUM( ATPASE IN RAT)

Phencyclidine hydrochloride (PCP) also known as Angel Dust is a very p otent psychotomimetic drug of abuse. Besides its central nervous syste m (CNS) effects PCP produces a number of adverse effects in a variety of tissues including the cardiovascular system. Since PCP is known to alter the cellular calcium homeostasis the present studies were initia ted to determine the changes in cardiac Ca2+ ATPase activity in rats t reated with PCP. For in vitro studies the cardiac sarcoplasmic reticul um (SR) fractions prepared from normal rats were incubated with 25, 50 and 100 mu M PCP and the enzyme activities were estimated. Whereas, f or in vivo studies the cardiac SR fractions prepared from rats treated with PCP (10 mg/kg body wt. single dose, intra-peritoneally (i.p.)) a nd sacrificed at different time intervals were used. PCP reduced the C a2+ ATPase activity significantly both in vitro and in vivo. A 50% inh ibition of the enzyme activity was obtained with 100 mu M PCP in vitro . A significant reduction of SR Ca2+ ATPase was also evident as early as 1 h after treatment of rats with PCP. The reduction of Ca2+ ATPase activity in SR was irreversible even at 12 h after treatment. The in v itro kinetic studies revealed, that PCP was found to be a competitive inhibitor of Ca2+ ATPase with respect to the substrate, ATP, and non-c ompetitive with respect to Ca2+ activation. These results indicate tha t PCP alters the myocardial Ca2+ homeostasis by inhibiting the Ca2+ AT Pase in cardiac SR in rats. Inhibition of SR Ca2+ ATPase may result in the impairment of contraction and relaxation coupling processes in th e myocardium. (C) 1998 Elsevier Science Ireland Ltd. All rights reserv ed.