INFLUENCE OF SOME RADIOPROTECTANT AGENTS ON THE ENZYME SYSTEM OF HEPATIC MICROSOMES DEGRADING HEXOBARBITAL (in French)
Tests were conducted on a preparation of rat liver microsomes which contain an enzyme system catabolizing barbiturates that requires the presence of oxygen and nicotinamide adenine dinucleotide (NAD). Assay of radioprotectants on this system was prompted by the previous unpublished finding that cysteamine prolonged barbiturate anesthesia. Oxidation of hexobarbital in rat liver homogenate, freed of mitochondriae and nuclei by 10-min centrifugation at 15000 g, at 37 deg C, and pH 7.4 was inhibited approximates 50% bv 1.5 mM cystamine or 1 mM 5-hydroxytryptamine. Histamine, at 2 to 3 mM, produced not more than 30 to 35% inhibition, and higher concentrations were even less inhibitory. Cysteamine was only about I/5th as inhibitory as cystamine, and this inhibition could be traced to its reduction to cystamine. In comparison, BETA -diethylaminoethyl diphenylpropyl acetate (SKFS25-A), a selective inhibitor of this microsomal enzyme system, at 0.2 mM caused 80 to 85% inhibition. None of the substances tested interfered with the reduction of NAD in the presence of glucose-6phosphate dehydrogenase, which is obtained in the soluble fraction of liver homogenate after centrifugation for 60 min at 105000 g. The microsomes catalyzed the reoxidation of reduced NAD by atmospheric oxygen, and this reaction was not inhibited by SKF 525-A after 6 min incubation. However, after 10 min, approximates 45% inhibition was noted. It was also inhibited by cysteamine and 5- hydroxytryptamine, to a similar extent by 1 and 5 mM concentrations, respectively. Cysteamine was only inhibitory after 15-min incubation, probably because of its prior conversion to cystamine. Histamine had an initial stimulatory and a final inhibitory action. It is concluded that the inhibitory action of radioprotective agents on this enzyme system is responsible for their prolongation of barbiturate anesthesia and that this effect is manifested via their inhibition of the reoxidation of reduced NAD. (BBB)
- Research Organization:
- Universite, Liege
- NSA Number:
- NSA-17-035415
- OSTI ID:
- 4670544
- Journal Information:
- Arch. Intern. Pharmacodyn., Vol. Vol: 142; Other Information: Orig. Receipt Date: 31-DEC-63
- Country of Publication:
- Country unknown/Code not available
- Language:
- French
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