COMPARISON BETA2 VS BETA1 ADRENOCEPTOR STIMULATION IN RAT CARDIOCYTE STIMULATION

β -肾上腺素能受体（β -肾上腺素能受体）的刺激具有深远的调节作用

Beta-adrenergic receptor (betaAR) stimulation has profound modulatory effects on the cardiac contraction. It has been well documented that both the beta1 and beta2 AR subtypes are coupled to adenylcyclase and that their stimulation by beta1 and beta2 AR specific agonist leads to an increase in cAMP. Stimulation of other heart cell receptors, e.g. prostaglandin, also leads to an increase in cAMP but has no effect on contraction, presumably because the cAMP pool affected is not associated with membranous cAMP activation and is not linked to heart cell Ca2+ regulation. It is widely recognized that stimulation of beta AR's leads to an increase in the particulate (membrane bound) cAMP levels and protein kinase (PK) phosphorylation of key proteins involved in excitation-contraction coupling. However, whether beta2 AR stimulation increases particulate cAMP and cAMP dependent phosphorylation is not known. In this regard we have recently shown that the beta2 AR mediated effects on Ca2+, contraction and L type Ca2+ channels in rat heart cells differ markedly from those elicited by beta1 AR stimulation. In this project we further demonstrated that the beta2 effects on Ca2+ and contraction in these cells are not mediated by cAMP. This conclusion is based on the measurement of total and particulate cAMP levels and the discoupling between the increase of cAMP levels and increases in cell contraction and Cai transient. Furthermore, phosphorylation of sarcoplasmic reticulum (SR) phospholamban was dramatically increased by beta1 AR stimulation, but not by beta2AR stimulation. Thus, beta1 and beta2AR are coupled to cellular effects of altered Ca2+ homeostasis and contraction via different signal transduction pathways.