Heredity of hexobarbital sleeping time and efficiency of drug metabolism in Wistar and Sprague-Dawley rats.
Nature of considerable variability of hexobarbital sleeping time and drug metabolism efficiency within a single strain of rats were investigated. Wistar or Sprague-Dawley rats with shorter than average hexobarbital sleeping time had also higher rates of in vitro hepatic microsomal metabolism of hexobarbital, aminopyrine, aniline and benzene, higher liver weight, microsomal protein content and P-450 level, and faster hexobarbital blood level decline (but similar volumes of distribution) after intraperitoneal hexobarbital sodium than those with relatively longer hexobarbital sleeping time, but awakened with the same hexobarbital blood level. The differences were maintained throughout the life of rats and inherited in their offspring. It indicated a possible genetic control of hexobarbital sleeping time and efficiency of drug metabolisms with apparent differences in selection response for Type I and Type II substrates (hexobarbital and aminopyrine vs aniline): it might indicate different heredity mechanism for these types of substrates. Stronger hexobarbital narcotic effect in females was associated with the rate of hexobarbital metabolism, but also with higher brain sensitivity. Hexobarbital sleeping time pattern indicated more general pattern of drug metabolism (better for Type I substrates) and success of selection of rats for different efficiency of drug metabolism (up to 8-fold differences in F5 generation) suggested considerable genetic non-homogeneity of two common strains of laboratory rats.
D000632:Aminopyrine / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001554:Benzene / Q000378:metabolism; D001711:Biotransformation; D001921:Brain / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005260:Female; D006591:Hexobarbital / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver; D008297:Male; D008862:Microsomes, Liver / Q000032:analysis / Q000201:enzymology; D008930:Mitochondria, Liver / Q000378:metabolism; D008967:Molecular Biology; D009929:Organ Size; D011506:Proteins / Q000032:analysis; D051381:Rats; D012737:Sex Factors; D012890:Sleep / Q000187:drug effects*; D013045:Species Specificity
D000814:Aniline Compounds; D011506:Proteins; D000632:Aminopyrine; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D001554:Benzene