Inhibition of acetylcholinesterase and different ATPases by a novel phosphorothionate (RPR-II) in rat brain

A novel phosphorothionate (2-butenoic acid-3-(diethoxy phosphinothioyl)-met hyl ester (RPR-II), synthesized at the Indian Institute of Chemical Technol ogy, Hyderabad, targets its effect on rat brain acetylcholinesterase (AChE) and Na+-K+, Mg2+, and Ca2+ ATPases, as evident in this investigation, Thre e sub-chronic doses 0.014 (low), 0.028 (medium), and 0.042 (high) mg kg(-1) mere administered to rats daily for a period of 90 days RPR-II caused stat istically significant dose- and time-dependent inhibition in brain AChE and also in Na+-K+, Mg2+, and Ca2+ ATPases in both male and female rats after 45 and 90 days of treatment, The low dose was generally insignificant while the medium and high doses were significantly effective. Females were more susceptible than males with regard to brain AChE, Na+-K+, and Mg2+ ATPases, which indicates sexual dimorphism in the treated rats. Interestingly, afte r 28 days post-treatment, recovery of these enzymes was observed. The relat ive sensitivities of these enzymes indicated that brain AChE was more sensi tive than any of the ATPases, but among the ATPases Na+-K+ ATPase,vas more susceptible than Ca2+ or Mg2+ ATPases. This compound, besides inhibiting th e target of organophosphates, AChE, also inhibited different ATPases, sugge sting both synaptic transmission and nerve conduction were affected. (C) 20 00 Academic Press.