Pub. Date : 1999 Sep
PMID : 10454503
9 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
1 | Several of the hepatic microsomal cytochromes P-450 (CYP) including CYP3A are inducible by phenobarbital (PB). | Phenobarbital | cytochrome P450, family 3, subfamily a, polypeptide 11 | Mus musculus |
2 | Several of the hepatic microsomal cytochromes P-450 (CYP) including CYP3A are inducible by phenobarbital (PB). | Phenobarbital | cytochrome P450, family 3, subfamily a, polypeptide 11 | Mus musculus |
3 | However, the intracellular pathways involved in the action of PB on CYP3A remain poorly known. | Phenobarbital | cytochrome P450, family 3, subfamily a, polypeptide 11 | Mus musculus |
4 | With the aim to unravel some of the main aspects of PB signaling, we first devised a simple model of mouse cultured primary hepatocytes in which CYP3A mRNA and protein were strongly induced by PB in the absence of dexamethasone and were at maximum levels after a 48-h treatment with a 2-mM dose of PB. | Phenobarbital | cytochrome P450, family 3, subfamily a, polypeptide 11 | Mus musculus |
5 | With the aim to unravel some of the main aspects of PB signaling, we first devised a simple model of mouse cultured primary hepatocytes in which CYP3A mRNA and protein were strongly induced by PB in the absence of dexamethasone and were at maximum levels after a 48-h treatment with a 2-mM dose of PB. | Phenobarbital | cytochrome P450, family 3, subfamily a, polypeptide 11 | Mus musculus |
6 | With the aim to unravel some of the main aspects of PB signaling, we first devised a simple model of mouse cultured primary hepatocytes in which CYP3A mRNA and protein were strongly induced by PB in the absence of dexamethasone and were at maximum levels after a 48-h treatment with a 2-mM dose of PB. | Phenobarbital | cytochrome P450, family 3, subfamily a, polypeptide 11 | Mus musculus |
7 | Under these culture conditions, we studied the effects of inhibitors and activators of different protein kinases or phosphatases on CYP3A mRNA and protein induction by PB. | Phenobarbital | cytochrome P450, family 3, subfamily a, polypeptide 11 | Mus musculus |
8 | Inhibition of Ca(2+)/calmodulin-dependent protein kinase by KN-62 or the intracellular Ca(2+) chelator BAPTA-AM produced an inhibition of CYP3A induction by PB. | Phenobarbital | cytochrome P450, family 3, subfamily a, polypeptide 11 | Mus musculus |
9 | Taken together, our results suggest that CYP3A induction by PB is regulated positively by calmodulin-dependent protein kinase and cGMP-dependent protein kinase, and negatively by PKA in mouse hepatocytes in primary culture. | Phenobarbital | cytochrome P450, family 3, subfamily a, polypeptide 11 | Mus musculus |