Alterations in adenylyl cyclase sensitivity to hormones in the brain, myocardium, and testes of rats immunized with BSA-conjugated peptide 269–280 of type 3 melanocortin receptor

摘要: Binding of the type 3 melanocortin receptors (M3R) functionally coupled to Gs proteins with α-melanocyte-stimulating hormone (α-MSH) or M3R agonist γ-MSH results in activation adenylyl cyclase (AC) brain, which is responsible for M3R-mediated regulation physiological and biochemical processes central peripheral nervous systems. A decrease activity leads energy metabolism disorders, metabolic syndrome, functional disturbances cardiovascular However, molecular mechanisms these alterations role signaling system (ACSS) are yet poorly understood. The aim this work was study effects a long-term (13 months, 8 injections) immunization male rats BSA-conjugated peptide A-[PTNPYCICTTAH269–280]-A (A-[269–280]-A), corresponding third extracellular loop rat M3R, on ACSS its by neurotransmitters hormones testes, myocardium. At end experiment, body weight animals decreased, specific mass adipose tissue increased, dyslipidemia observed, sensitivity insulin reduced spite increase secretion response glycemic load. In brain immunized rats, AC-stimulating γ-MSH, noradrenaline, serotonin PACAP-38 stimulating effect dopamine AC-inhibiting 5-nonyloxytryptamine (an 5-hydroxytryptamine receptor (5-HTR) 1B/1D subtype) while M3R/M4R α-MSH M4R THIQ remained unchanged. myocardial membranes, stimulation AC agonists β3-adrenergic (β3-AR) enhanced, β1- β2-agonists were attenuated relaxin weakened. testicular chorionic gonadotropin as well GppNHp (non-hydrolysable GTP analog). These data indicate that attenuation considerable playing key functioning nervous, reproductive observed myocardium testes characterized hormonal specificity. Identification disorders one approaches studying etiology pathogenesis diseases associated inhibition M3R-melanocortin brain.