Effect of pentobarbital dependence on adenylate cyclase activity and calmodulin levels in rat cerebral cortex.
The effect of calcium (Ca2+) on the adenylate cyclase activity and calmodulin level of cerebral cortex was determined in pentobarbital dependent rats and age matched controls. Female Sprague-Dawley rats were made dependent and maintained on pentobarbital by eating a mixture of pentobarbital and rat chow (350 mg pentobarbital/30 g chow). Ca2+ activated then inhibited the adenylate cyclase activity associated with a 20,000 X g particulate fraction from pentobarbital dependent and age matched control rats. The values for one-half maximal stimulation and inhibition by Ca2+ did not differ significantly in either cortical preparation. However, the ability of Ca2+ to activate adenylate cyclase from pentobarbital dependent animals was significantly decreased (p less than 0.05) when compared to control animals. Pentobarbital (10(-4) - 10(-3) added to particulate fractions from naive control rats did not alter the ability of Ca2+ to activate adenylate cyclase. The calmodulin levels in the particulate fraction from pentobarbital dependent animals (30.2 +/- 6.7 ng calmodulin/mg protein) did not differ significantly when compared to control (33.0 +/- 4.7 ng/mg). By contrast, the calmodulin levels (37.9 +/- 5.9 ng/mg) in the 20,000 X g supernatant from cortex of pentobarbital dependent animals was significantly greater than the level in the supernatant from control animals (28.6 +/- 2.6 ng/mg). The ability of forskolin, dopamine, GTP or forskolin plus GTP (all at a concentration of 100 microM) to activate adenylate cyclase was significantly decreased in particulate preparations from pentobarbital dependent animals. In summary, our data show that alterations in calmodulin levels and a decreased responsivity of adenylate cyclase occur in animals physically dependent on pentobarbital.
D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000032:analysis*; D002540:Cerebral Cortex / Q000032:analysis*; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D010424:Pentobarbital; D051381:Rats; D011919:Rats, Inbred Strains; D019966:Substance-Related Disorders / Q000378:metabolism*
D002147:Calmodulin; D004224:Diterpenes; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D010424:Pentobarbital; D002118:Calcium; D004298:Dopamine