140 PHOSPHATES AND THERAPEUTIC AGENTS 



5 X 10"* M decreased levels of phosphocreatine in slices of 

 guinea pig cerebral cortex from 1-5 /xmoles/g to l-O/xmoles/g but 

 also decreased the oxygen uptake by 10-12%. Higher concentra- 

 tions of 10~^M decreased phosphate levels and oxygen uptake still 

 further (Buchel and Mcllvv^ain, 1950). Similar results were 

 obtained w^hen soneryl (5-butyl-5-ethyl barbituric acid) and dial 

 (5 : 5-diallyl barbituric acid) were used at concentrations of 

 10-2-10-3 M (Mcllwain and Buchel, 1951). On the other hand 

 chloral at 10"* M was without effect upon oxygen uptake or levels 

 of phosphocreatine though this concentration is fully sedative 

 in vivo. Decrease in levels of energy-rich phosphates are also 

 brought about by the convulsants, picrotoxin, strychnine and 

 pentamethylene tetrazole at lO-^-lQ-^M, reducing the levels of 

 phosphocreatine parallel with reductions in the oxygen uptake of 

 guinea pig cerebral slices (Anguiano and Mcllwain, 1951). 



Some interesting effects of tranquillizing agents and depressants 

 upon the incorporation of radioactive phosphate into the phospho- 

 lipids and other phosphates have been noted by Magee et al. 

 (1956). Thus, chlorpromazine at 10" ^-10-^ M and azacyclonol at 

 10-3 M, concentrations which did not alter the oxygen uptake of 

 the slices, increased the radioactivity of the inositol phosphatides, 

 phosphatidic acids and glycerylphosphorylserine by 100%, the 

 radioactivity of the other phospholipids being unaffected. Curi- 

 ously, no changes were detected either in the quantities or specific 

 radioactivities of phosphocreatine and adenosine triphosphate. 

 The results are puzzling, for present evidence implicates adenosine 

 triphosphate as the primary source of phosphorus in cerebral 

 phospholipids. It is difficult to see how an increase in radioactivity 

 of the product could be accomplished without an increase in the 

 radioactivity of the precursor. 



An impaired ability to maintain normal levels of energy-rich 

 phosphates when the oxygen uptake is suppressed is indicative of 

 the inability of the oxidative phosphorylation to keep pace with the 

 energy requirements of the tissue. In such situations it seems 

 reasonable to expect the incorporation of radioactive phosphate 

 into phosphorus derivatives such as the phospholipids, also to be 

 decreased. At concentrations of 10 -^M, pentobarbitone and 

 chloretone inhibited the incorporation of radioactive phosphate 

 into the phospholipids, nucleic acids and phosphoproteins of 

 cerebral slices by 60-80% of the control values (Strickland, 1954; 



