Long‐Chain Acylcarnitines Mediate the Hypoxia‐Induced Increase in α1‐Adrenergic Receptors on Adult Canine Myocytes
Long‐Chain Acylcarnitines Mediate the Hypoxia‐Induced Increase in α1‐Adrenergic Receptors on Adult Canine Myocytes
复制标题
长链酰基肉碱介导缺氧诱导的成年犬肌细胞α1肾上腺素受体的增加
作者：
G. Heathers;Kathryn A. Yamada;Evelyn M. Kanter;P. Corr
为了阐明体内缺血时α1-肾上腺素能受体增加的机制，我们开发了一种测量分离的、钙耐受的成年犬肌细胞中α1-肾上腺素能受体的方法。特异性[3 H]哌唑嗪结合是快速、可饱和、可逆的，并证明了α1-肾上腺素能受体的预期效价和立体特异性顺序。在25± C缺氧30分钟或在37± C缺氧10分钟的心肌细胞，α1-肾上腺素能受体的数量增加2 - 3倍，而受体亲和力无显著变化。在37±C下再给氧10分钟，缺氧诱导的受体数量增加是可逆的。相比之下，更长时间的缺氧80分钟或低渗休克，实际上减少受体数量低于含氧量正常，控制值。长链酰基肉毒碱在心肌细胞中的浓度也增加了三倍，暴露于缺氧30分钟。2-[5-（4-氯苯基）-戊基]-环氧乙烷-2-羧酸钠（波卡，10 μM）是一种肉毒碱酰基转移酶I的有效抑制剂，它不仅能消除长链酰基肉毒碱的积累，还能消除缺氧30分钟引起的α1-肾上腺素能受体数量的增加。同样，含氧量正常的细胞与外源性棕榈酰肉毒碱（1 μM）孵育10分钟，在存在或不存在波卡的情况下，也增加了α1-肾上腺素能受体的数量。因此，缺氧导致与内源性长链酰基肉毒碱增加相关的α1-肾上腺素能受体增加。此外，肉毒碱酰基转移酶I的抑制不仅防止长链酰基肉毒碱的肌膜积累，而且还防止α1-肾上腺素能受体的暴露，这表明内源性长链酰基肉毒碱的积累对缺氧诱导的成人肌细胞上α1-肾上腺素能受体的增加至关重要。（《循环研究》，1987年;61：735-746）
To elucidate the mechanisms responsible for the increase in α1-adrenergic receptors during ischemia in vivo, we developed a procedure for measuring α1-adrenergic receptors in isolated, calcium-tolerant adult canine myocytes. Specific [3H]prazosin binding was rapid, saturable, reversible, and demonstrated the expected order of potency and stereospecificity for the α1-adrenergic receptor. Myocytes exposed to 30 minutes of hypoxia at 25± C or only 10 minutes at 37± C exhibited a twofold to threefold increase in the number of α1-adrenergic receptors with no significant change in receptor affinity. This hypoxia-induced increase in receptor number was reversible by 10 minutes of reoxygenation at 37±C. In contrast, more prolonged hypoxia of 80 minutes or hypotonic shock actually decreased receptor number below normoxic, control values. The concentration of long-chain acylcarnitines in myocytes also increased threefold on exposure to 30 minutes of hypoxia. Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA, 10 μM), a potent inhibitor of carnitine acyltransferase I, not only abolished the accumulation of long-chain acylcarnitines but also the increase in α1-adrenergic receptor number induced by 30 minutes of hypoxia. Likewise, incubation of normoxic cells with exogenous palmitoyl carnitine (1 μM) for 10 minutes also increased α1-adrenergic receptor number in the presence or absence of POCA. Thus, hypoxia results in an increase in α1-adrenergic receptors associated with an increase in endogenous long-chain acylcarnitines. Furthermore, inhibition of carnitine acyltransferase I prevents not only the sarcolemmal accumulation of long-chain acylcarnitines but also the exposure of the α1-adrenergic receptor, indicating that accumulation of endogenous long-chain acylcarnitines is critical to the hypoxia-induced increase in α1-adrenergic receptors on adult myocytes. (Circulation Research 1987;61:735-746)
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DOI：
10.1152/ajpheart.1982.243.2.h187
发表时间：
1982
期刊：
The American journal of physiology
影响因子：
--
作者：
Corr,PB;Snyder,DW;Lee,BI;Gross,RW;Keim,CR;Sobel,BE
通讯作者：
Sobel,BE
缺氧、钙流动和正性肌力状态：培养心脏细胞的研究。
影响因子：
4.8
作者：
Smith,TW;Barry,WH;Marsh,JD;Lorell,B
通讯作者：
Lorell,B
缺血心肌流出物中的溶血磷酸甘油酯及其致心律失常作用的增强。
DOI：
10.1152/ajpheart.1981.241.5.h700
发表时间：
1981
期刊：
The American journal of physiology
影响因子：
--
作者：
Snyder,DW;CraffordJr,WA;Glashow,JL;Rankin,D;Sobel,BE;Corr,PB
通讯作者：
Corr,PB
L-棕榈基肉碱和钙离子对禽类心室肌的兴奋性离子电流的作用类似。
影响因子：
20.1
作者：
Inoue,D;Pappano,AJ
通讯作者：
Pappano,AJ
3h-P物质与唾液腺膜结合。
影响因子：
3.6
作者：
Lee,CM;Javitch,JA;Snyder,SH
通讯作者：
Snyder,SH