[Adrenergic regulation of the mammalian heart]

Adrenergic system in the mammalian heart plays a pivotal role in regulation of contractility and/or heart rate. At present, nine subtypes of adrenergic receptors (AR) have been identified. Among these there are six AR localized in the plasma membrane of cardiomyocytes. They mediate their effects by increases in the intracellular level of various signaling molecules which initiate diverse cellular responses. The effects of stimulation of both beta-AR by catecholamines noradrenaline and adrenaline are consistent with coupling to the Gs protein-adenylyl cyclase-cAMP-protein kinase classical pathway, with consequent protein kinase A-catalysed phosphorylation of target enzymes responsible for increased contractility and hastening of relaxation. In contrast to beta1-AR, beta2-AR can also couple to G(i) protein which causes cAMP-independent control of calcium signaling and contraction. Activation of beta-AR obviously couples to a G(i)/ nitric oxide pathway and mediates a decrease in contractile force, whereas stimulation of alpha-AR increases contractility via G protein/phospholipase C/diacylglycerol/inositoltrisphosphate/protein kinase C pathway. These findings reveal the diversity and specifity of AR subtypes and G protein interactions. They also provide new insights in understanding the differential regulation and functionality of AR subtypes in healthy and diseased hearts.