Inhibition of calcium ATPase by phencyclidine in rat brain

Phencyclidine (PCP) is a potent psychotomimetic drug of abuse and has profo und effect on the functioning of the central nervous system (CNS). Many of the CNS functions are known to be mediated by calcium (Ca2+). In the presen t study we have investigated the effects of PCP on Ca2+ ATPase activity in rat brain both in vitro and in vivo. For in vitro studies, synaptic membran e fractions prepared from normal rat brain were incubated with PCP at diffe rent concentrations (25-100 mu M) before the addition of substrate. For n v ivo studies, rats were treated with a single moderate dose of PCP (10 mg/kg , IP) and animals were sacrificed at 1,2, 6 and 12 h after treatment. Ca2ATPase activity in synaptic membrane fractions was assayed by estimation of inorganic phosphate. PCP inhibited the Ca2+ ATPase in vitro in a concentra tion dependent manner with significant effect at 50 and 100 mu M. A signifi cant time-dependent reduction of the Ca2+ ATPase activity was evident in vi vo. As early as 2 h after the treatment of rats with PCP the ATPase activit y was significantly reduced. The reduction of Ca2+ ATPase observed even at 12 h after treatment suggesting a prolonged presence of the drug in the bra in tissue. Further, kinetic studies in vitro indicated PCP to be a competit ive inhibitor of Ca2+ ATPase with respect to the substrate, ATP. The presen t findings indicate that PCP inhibits synaptic membrane Ca2+ ATPase thus al tering cellular Ca2+ homeostasis in CNS which may partially explain the pha rmacological effects of the drug and/or its neurotoxicity.