148 



PHOSPHATES AND THERAPEUTIC AGENTS 



brain was detectable in animals anaesthetized with phenobarbitone 

 (Carr et al., 1955). 



The effect of phenobarbitone upon the rate of resynthesis of 

 phosphocreatine was examined in cerebral slices in which the 

 levels of phosphocreatine had been first decreased by electrical 

 pulses applied for a few seconds. It was found that pheno- 

 barbitone at 1-7 X 10" ^M had no effect upon the resynthesis which 

 proceeded at the same rate (140-150 /xmoles/g hr-^) as in the 

 absence of phenobarbitone (Fig. 17). These two effects, a decreased 

 rate of breakdown and an unimpaired rate of synthesis of phospho- 

 creatine point to an action which prevents the tissue from utilizing 



Table 23. — Phenobarbitone on the Breakdown of Phosphocreatine 



IN Cerebral Slices Subjected to Electrical Stimulation 



(Values are levels of phosphocreatine in /xmoles/g wet wt.) 



Data from Cohen and Heald (1960). Slices were incubated in oxygenated 

 saline at 37-5 °C and stimulated with condenser pulses, 15V peak potential, 

 0-4-0-5 msec duration. 



its energy-rich phosphates in response to stimulus, a situation 

 similar to that considered to apply during anaesthesia in vivo 

 (p. 46). A more detailed examination of this process was made 

 with slices metabolizing radioactive phosphate in the system 

 described in Chapter 4 (p. 116). Cerebral slices were incubated 

 in the presence of 1-7 X 10"^ M phenobarbitone for 30 min, 

 radioactive phosphate was added and 3 min later the slices were 

 removed, washed and transferred to fresh non-radioactive saline 

 containing phenobarbitone. After a further 2 min the radio- 

 activity of the phosphates was determined. It was found that the 

 specific radioactivity of inorganic phosphate, phosphocreatine 

 adenosine triphosphate and the phosphoprotein fraction were all 

 considerably higher than the specific radioactivity of similar 



