The brain dopaminergic system as an important center regulating liver cytochrome P450 in the rat

Abstract

This paper reviews evidence that changes in the functioning of the brain dopaminergic system affect liver cytochrome P450 (CYP) expression (CYP1A, CYP2B, CYP2C11 and CYP3A in the case of the tuberoinfundibular pathway or CYP1A and CYP3A in the case of the mesolimbic pathway), as well as blood plasma concentration of the respective pituitary hormones in the rat. Thus, the brain dopaminergic system has been established as an important center regulating the liver CYP. This regulation proceeds through the dopaminergic D2 receptors of the pituitary (activated by the tuberoinfundibular pathway) and the D2 receptors of the nucleus accumbens (activated by the mesolimbic pathway and conveying a message from the nucleus accumbens to the paraventricular nucleus of the hypothalamus). These receptors directly (GH) or indirectly (CRH → ACTH → corticosterone; TRH → TSH → T3) stimulate the secretion of hormones, which activate nuclear/cytosolic receptors controlling CYP genes. Thus, the prediction of neuroactive drug action on hepatic CYP and drug–drug interactions on the basis of in vitro studies only is not sufficient, because such an experimental model does not allow the central neuroendocrine regulation of the enzyme.