Роль меланокортиновой системы в регуляции стрессорного ответа

Abstract

In mammals and other vertebrates the effect of melanocortin peptides is promoted by five types of melanocortin receptors (MCR), connected with G-protein-dependent mechanisms and the activation of cAMP in the cells. The brain exhibits the expression of two types of receptors MCR3 and MCR4, the functional activity of which is controlled by AgRp (agouti gene related peptide), the endogenous antagonist of these types of receptors. The expression of AgRp was indicated in the neurons of the arcuate nucleus of the hypothalamus. The expression of MCR3 and MCR4 was shown in different brain neurons, in particular in dopaminergic, noradrenergic and serotonergic neurons. These data indicate the morphofunctional interrelation of the melanocortin and the monoaminergic systems of the brain. The current paper discusses the dose-dependent inhibitory effect of the active fragments of AgRp (83-132 and 25-51) on the functional activity of monoaminergic neurons in the brain, and, correspondingly, the biosynthesis of monoamines, which is realized via G-protein-dependent and G-protein-independent intracellular mechanisms. The inhibitory effects of AgRp active fragments on the biosynthesis of monoamines can be considered as a protective mechanism, which is activated by corticosteroids in times of prolonged stress in order to reduce the activity of monoaminergic neurons and, apparently, other brain neurons that express MCR.