Adenosine A2a-receptor activation enhances cardiomyocyte shortening via Ca2+-independent and -dependent mechanisms.
Adenosine A2a-receptor activation enhances cardiomyocyte shortening via Ca2+-independent and -dependent mechanisms.
复制标题
腺苷 A2a 受体激活通过 Ca2 独立和依赖机制增强心肌细胞缩短。
DOI：
10.1152/ajpheart.1999.276.5.h1434
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
DobsonJr,JG
中科院分区：
文献类型：
--
作者：
Woodiwiss,AJ;Honeyman,TW;Fenton,RA;DobsonJr,JG
腺苷A2a受体(A2aR)刺激可促进心肌细胞的缩短。用钙离子敏感的荧光染料Fura 2-AM研究了A2aR介导的心肌细胞收缩能力的增加是否与细胞内钙瞬变的幅度变化有关。在存在完整的抑制性G蛋白通路的情况下，A2aR激动剂10 2-p-(2-carboxyethyl)phenethyl-amino-5′-N-ethylcarboxamidoadenosine(10−4M CGS-21680)使钙瞬变增加8±5%，而心肌细胞缩短增加54±1%。相反，2×10−7M异丙肾上腺素(β-肾上腺素能受体激动剂)使钙瞬变增加104±15%，使心肌细胞缩短61±6%。在经百日咳毒素或腺苷A1受体拮抗剂8-环戊基-1，3-二丙基黄嘌呤(DPCPX)阻断腺苷抗肾上腺素能作用的心肌细胞上刺激A2aR时，钙瞬变的最大增加幅度相似(PTX：10−4M CGS-21680，14±6%；10−4M ADO，15±4%；无PTX：10−5M ADO+2×10−7M DPCPX，19±1%)。这些结果表明，与显著增加心肌细胞钙瞬变和缩短的β-肾上腺素能刺激相比，A2aR介导的心肌细胞缩短的增加仅伴随着轻微的钙瞬变增加。这些观察结果表明，A2aR的收缩效应主要是通过钙非依赖性的变力机制来实现的。
Adenosine A2areceptor (A2aR) stimulation enhances the shortening of ventricular myocytes. Whether the A2aR-mediated increase in myocyte contractility is associated with alterations in the amplitude of intracellular Ca2+transients was investigated in isolated, contracting rat ventricular myocytes using the Ca2+-sensitive fluorescent dye fura 2-AM. In the presence of intact inhibitory G protein pathways, 10−4M 2-p-(2-carboxyethyl)phenethyl-amino-5′-N-ethylcarboxamidoadenosine (CGS-21680), an A2aR agonist, insignificantly increased Ca2+transients by 8 ± 5%, whereas myocyte shortening increased by 54 ± 1%. In contrast, 2 × 10−7M isoproterenol, a β-adrenergic receptor agonist, increased Ca2+transients by 104 ± 15% and increased myocyte shortening by 61 ± 6%. When A2aR were stimulated in myocytes that had the antiadrenergic actions of adenosine (Ado) abolished by either treatment with pertussis toxin (PTx) or the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1-receptor antagonist, the maximum increases in Ca2+transients were similarly nominal (with PTx: 10−4M CGS-21680, 14 ± 6% and 10−4M Ado, 15 ± 4%; without PTx: 10−5M Ado + 2 × 10−7M DPCPX, 19 ± 1%). These results indicate that compared with β-adrenergic stimulation, which markedly increases myocyte Ca2+transients and shortening, A2aR-mediated increases in myocyte shortening are accompanied by only modest increases in Ca2+transients. These observations suggest that the A2aR-induced contractile effects are mediated predominantly by Ca2+-independent inotropic mechanisms.