抄録
The sympathetic nervous system is a major mechanism of regulating cardiac function. Norepinephrine released from the synaptic terminal binds to beta-adrenergic receptors on the cardiac cell membrane, leading to the activation of G protein and adenylyl cyclase. cAMP produced by adenylyl cyclase initiates a cascade of phosphorylation reaction within the cardiac myocyte, leading to increased cardiac contractility and rate. The heart is known to express two major adenylyl cyclase isoforms, namely type 5 and type 6 isoforms. Type 5 adenylyl cyclase is a major isoform in adult hearts while type 6 in neonatal hearts. From various in vitro and in vivo studies in recent years, using transgenic or gene-targeted models as well as newly developed selective regulatory compounds for such isoforms, it has been shown that the two isoforms may play opposite roles in regulating cardiac myocyte viability and thus function as shown under various pathophysiological conditions. Activation of the type 5 isoform leads to increased cardiac contractility while prolonged activation may deteriorate cardiac function through increased cardiac myocyte apoptosis. In contrast, activation of the type 6 isoform plays protective roles for the heart, which has been shown in various animal models with the type 6 gene transfer. Disruption of type 5 isoform is now shown to protect the heart from various pathophysiological stresses, and to increase longevity. We will discuss potential molecular mechanisms for such differences between the adult and the neonatal isoforms in the heart. [J Physiol Sci. 2008;58 Suppl:S45]
