title: Induction of new carbonic anhydrase II following treatment with acetazolamide in DBA and C57 mice.
abstract: The mechanism by which animals develop tolerance to the antiepileptic effects of the carbonic anhydrase (CA) inhibitor, acetazolamide, was explored using a quantitative immunocytochemical method. Cerebral cortex sections of DBA/2J mice susceptible to audiogenic seizures and of C57BL/6J nonsusceptible mice were stained with antibody to mouse CA II in controls and following treatment with acetazolamide (40 and 200 mg/kg) for 1, 3, and 5 days. The percentage increases in CA II fluorescent intensity of cells from C57 mice treated with 40 and 200 mg/kg acetazolamide over those of untreated mice were 22 and 36%, respectively, after 1 day, 32 and 40%, respectively, after 3 days, and 17 and 40%, respectively, after 5 days of treatment. The corresponding percentage increases in fluorescent intensity of cells from DBA mice over controls were 13 and 32%, respectively, after 1 day, 17 and 41%, respectively, after 3 days, and 26 and 58%, respectively, after 5 days of treatment. The fluorescent intensity of cells from untreated DBA mice was 35% greater than those of untreated C57 mice. In C57 mice the maximum amount of CA II per cell at each dose occurred 24 h after acetazolamide treatment, whereas the amount in DBA mice continued to increase with time and dose up to 5 days. The differences between the two strains can be explained by changes in distribution of CA II to subcellular locations or by defects in phosphorylation of the molecule.
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D002540:Cerebral Cortex / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000378:metabolism*; D008811:Mice, Inbred DBA / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D002256:Carbonic Anhydrases; D000086:Acetazolamide