Differential effects of phenobarbital on the constitutive and inducible expression of P4502B and 3A subfamilies in sheep tissues

The activity and expression of cytochromes P450 were determined in liver, k idneys, lungs, duodenum, jejunum, ileum, and caecum of adult Lacaune sheep. High expression of total P450, benzphetamine and erythromycin demethylase activities, and P450 2B isoforms, as two distinct proteins that were detect ed and called P4502 Bm and P4502 Bx, was found in the lungs (in addition to liver). By contrast, the P450 3A subfamily was only expressed in liver and duodenal mucosa of untreated sheep. Phenobarbital (PB) treatment led to si gnificant increases in all measured hepatic parameters and in total P450 of each investigated organ with the exception of ileum and caecum. Benzphetam ine demethylase activity increased in liver and kidneys, correlating with t he expression of the two P450 2B proteins, which were also induced in duode num and ileum. By contrast, benzphetamine demethylase activity and expressi on of the P450 2B isoforms in lungs were unchanged by PB treatment. Erythro mycin demethylation activity and P450 3A subfamily expression was increased only in liver of PB-treated sheep.