CAJ | 학술논문

尽管β1和β2亚型肾上腺素能受体在结构和功能上十分相似，作者最近的研究显示这两种受体亚型在心肌细胞上的信号传递机制有很大的不同。β1受体激活后，启动经典的刺激性G蛋白-腺苷酸环化酶-环磷酸腺苷-蛋白激酶A的线性信号传导途径；而β 2受体除与刺激性G蛋白耦联外，还与抑制性G蛋白，Gi2和Gi3，耦联。β2受体与抑制性G蛋白的耦联在很大程度上决定了β受体亚型在心脏钙调控、收缩力、环磷酸腺苷水平和蛋白磷酸化上的不同作用。β2受体激活所引起的细胞内钙和收缩力的增加与细胞内环磷酸腺苷的增加和胞浆蛋白磷酸化有明显的脱节。这主要由于抑制性G蛋白激活的蛋白脱磷酸酶可以使 β2受体诱导的环磷酸腺苷-蛋白激酶A的作用局限于细胞质膜上。这种格局化作用，使公用的第二信使，环磷酸腺苷，在不同的β受体亚型激活时，选择性地执行不同的功能。新的证据表明，β受体亚型不仅在激动剂激活时表现不同，而且自发激活的能力也不同。另外，自发激活的β2受体和激动剂激活的β2受体在细胞内信号传递和靶蛋白的特异性上都不同。这些发现不仅进一步揭示了β受体亚型在信号传递上的多样性和特异性，而且为理解β受体亚型在健康和疾病状态下的调节和功能提供了新的线索。
진관β1화β2아형신상선소능수체재결구화공능상십 분상사，작자최근적연구 현시저량충수체아형재심기세포상적신호전체궤제유흔대적불동。β1수체격활후，계동 경전적자격성G단백-선감산배화매-배린산선감-단백격매A적선성신호전도도경；이β 2수체제여자격성G단백우련외，환여억제성G단백，Gi2화Gi3，우련。β2수 체여억제성G단백 적우련재흔대정도상결정료β수체아형재심장개조공、수축력、배린산선감수평화단백린 산 화상적불동작용。β2수체격활소인기적세포내개화수축력적증가여세포내배린산선감적 증가화포장단백린산화유명현적탈절。저주요유우억제성G단백격활적단백탈린산매가이사 β2수체유도적배린산선감-단백격매A적작용국한우세포질막상。저충격국화작용，사공 용적제이신사，배린산선감，재불동적β수체아형격활시，선택성지집행불동적공능。신적 증 거표명，β수체아형불부재격동제격활시표현불동，이차자발격활적능력야불동。령외，자 발격활적β2수체화격동제격활적β2수체재세포내신호전체화파단백적특이성상도불동 。저사발현불부진일보게시료β수체아형재신호전체상적다양성화특이성，이차위리해β수 체아형재건강화질병상태하적조절화공능제공료신적선색。
Although β1-adrenergic receptor (β1-AR) and β2- AR share a high degree of structural and functional similarities, our recent stu dies have revealed distinctive β-AR subtype signaling mechanisms in cardiac myocytes. While the classical linear stimulatory G protein (Gs)-adenylyl cyclase-cAMP-protein kinase A (PKA) signaling casc ade has been corroborated for β1-AR stimulation, the β2-AR signaling pathwa y bifurcates at the very first postreceptor step, the G protein level. In addition to Gs, β2-AR cou ples to pertussis toxin-sensitive inhibitory G protein (Gi), proteins Gi2 and Gi3. The coupling of β2-AR to Gi proteins mediates, to a large extent, the differential actions of the β-A R subtypes on cardiac Ca2+ handling, contractility, cAMP accumulation, and PKA-mediated protein phosphorylation. There is an apparent dissociation of β2-AR-induced augment ations of the intracellular Ca2+ (Cai) transient and contractility from cAMP p roduction and PKA-dependent cytoplasmic protein phosphorylation. This can be largely explained by Gi-protein phosphatase dependent functional compartmentalization of the β2-AR- directed cAMP/PKA signaling to the sarcolemmal microdomain. This compartmentalization allows the common second messenger, cAMP, to perform selective functions during β-AR subtype stimulation. Emerging evidence also points to distinctive property of β-AR subtypes to undergo spontaneous activation. Furthermore, spontaneously activated β2-AR is different from agonist-activated β2-AR in intracellular signaling and ta rget protein specificity. These findings not only reveal the diversity and specificity of β -AR subtype signaling, but also provide new insights for understanding the differential regu lation and functionality of β-AR subtypes in healthy and diseased hearts.