A phorbol ester has dual actions on the mechanical response in the rabbit mesenteric and porcine coronary arteries.

A phorbol ester has dual actions on the mechanical response in the rabbit mesenteric and porcine coronary arteries.
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佛波酯对兔肠系膜和猪冠状动脉的机械反应具有双重作用。

DOI:
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发表时间:
1986
期刊:
Journal of Physiology
影响因子:
--
通讯作者:
K. Sumimoto
K. Sumimoto
中科院分区:
--
文献类型:
--
作者:
T. Itoh;Y. Kanmura;H. Kuriyama;K. Sumimoto

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为阐明蛋白激酶C在机械反应中的作用,观察了蛋白激酶C激活剂12-O-十四酰佛波醇-13-乙酸酯(TPA)对完整和有皮肤的兔肠系膜动脉的作用。TPA(0.1微米)对K+引起的收缩具有双重作用(先增强后抑制)。39 mM-K+时增强作用明显,128 mM-K+时则以抑制为主。在使用A23187(1微米)后,在含有2 mM-EGTA的无钙溶液中加入2.6 mM-Ca~(2+),产生收缩。TPA在这种钙离子诱导的收缩中表现出相同的双重作用。在化学皮肤肌肉中,TPA增加了低浓度(0.1-0.3微米)钙离子引起的收缩幅度,但降低了高浓度(1-10微米)钙离子引起的收缩幅度。在磷脂酰丝氨酸(PS)存在下,TPA的这两种作用都被促进。在含有10 mM-EGTA和4 mM-mgATP的松弛液中,加入PS的TPA对加入腺苷-5-o-3-硫代三磷酸和0.3微米-Ca~(2+)所引起的非钙依赖性收缩无影响。在皮肤或完整的肌肉组织中应用TPA和PS,并不改变从咖啡因诱导的收缩幅度估计的细胞中存储的钙离子的量。本文研究了TPA对从猪冠状动脉制备的分散细胞悬液中Quin-2荧光强度测量的钙瞬变的影响。TPA对高K+时的钙瞬变无影响,但使收缩幅度增加。39 mM-K+在完整肌肉组织中引起的紧张性反应与0.3微米-Ca~(2+)在皮肤中引起的收缩反应的幅度基本相同。TPA加PS使两种收缩的幅度均有相同程度的增强。根据以上结果,我们认为TPA在收缩机制上具有双重作用,可能作用于收缩蛋白的调节系统。TPA的兴奋和抑制作用均依赖于钙离子浓度。然而,根据TPA的作用估计的蛋白激酶C的生理作用似乎与对收缩机械的兴奋作用有关。
To clarify the role of protein kinase C in the mechanical response, the effects of 12‐o‐tetradecanoylphorbol‐13‐acetate (TPA), an activator of protein kinase C, were investigated on intact and skinned smooth muscle preparations of the rabbit mesenteric artery. TPA (0.1 microM) showed dual actions (initial enhancement followed by inhibition during long exposure) on the K+‐induced contraction. The enhancement was marked in the presence of 39 mM‐K+ but inhibition was the predominant effect in the presence of 128 mM‐K+. Addition of 2.6 mM‐Ca2+ to a Ca2+‐free solution containing 2 mM‐EGTA following application of A23187 (1 microM), produced contraction. TPA showed the same dual actions on this Ca2+‐induced contraction. In chemically skinned muscles, TPA increased the amplitude of Ca2+‐induced contractions evoked by low concentrations of Ca2+ (0.1‐0.3 microM), but reduced those evoked by high concentrations of Ca2+ (1‐10 microM). Both actions of TPA were facilitated in the presence of phosphatidylserine (PS). TPA with PS had no effect on the Ca2+‐independent contraction evoked in relaxing solution containing 10 mM‐EGTA and 4 mM‐Mg ATP following application of adenosine‐5‐o‐3‐thiotriphosphate (ATP gamma S) and 0.3 microM‐Ca2+. The amount of Ca2+ stored in cells estimated from the amplitude of the caffeine‐induced contraction was not modified by application of TPA with PS in skinned or intact muscle tissues. The effects of TPA were investigated on the Ca2+ transient measured from the intensity of fluorescence of quin‐2 in dispersed cell suspensions prepared from the porcine coronary artery. TPA had no effect on the Ca2+ transient in high K+ but enhanced the amplitude of the contraction. Amplitudes of the tonic response evoked by 39 mM‐K+ in intact muscle tissues and the contraction induced by 0.3 microM‐Ca2+ in skinned muscle were much the same. TPA with PS enhanced the amplitudes of both contractions to the same extent. From the above results, we concluded that TPA shows dual actions on the contractile machinery and may act on the regulatory systems of contractile proteins. Both excitatory and inhibitory actions of TPA depended on the concentration of Ca2+. However, the physiological action of protein kinase C as estimated from the action of TPA seems to be related to an excitatory action on the contractile machinery.
DOI: 10.1073/pnas.81.21.6899
发表时间: 1984-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
BARON, CB;CUNNINGHAM, M;COBURN, RF
通讯作者: COBURN, RF
DOI: 10.1126/science.6231726
发表时间: 1984-01-01
期刊: SCIENCE
影响因子: 56.9
作者:
MCPHAIL, LC;CLAYTON, CC;SNYDERMAN, R
通讯作者: SNYDERMAN, R
DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
作者:
Iwasa,Y;Hosey,MM
通讯作者: Hosey,MM