Regulation of force and intracellular calcium transients by cyclic AMP generated by forskolin, MDL 17,043 and isoprenaline, and its modulation by muscarinic receptor agents: a novel mechanism for accentuated antagonism.
Regulation of force and intracellular calcium transients by cyclic AMP generated by forskolin, MDL 17,043 and isoprenaline, and its modulation by muscarinic receptor agents: a novel mechanism for accentuated antagonism.
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毛喉素、MDL 17,043 和异丙肾上腺素产生的环 AMP 对力和细胞内钙瞬变的调节，及其通过毒蕈碱受体剂的调节：一种增强拮抗作用的新机制。
DOI：
10.1007/bf02650348
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发表时间：
1989
影响因子：
9.5
通讯作者：
Endoh,M
中科院分区：
文献类型：
--
作者：
Endoh,M
用钙敏感生物发光蛋白Aequorin显微注射犬离体室小梁和兔乳头状肌，研究了细胞内钙瞬变与环磷酸腺苷水平升高或降低时细胞内钙瞬变与等长收缩的关系。Forsklin、MDL 17,043和异丙肾上腺素均能升高组织环磷酸腺苷水平，持续增加峰信号和力值，并以浓度依赖的方式缩短两种信号的持续时间。当将异丙肾上腺素的作用与改变细胞外钙离子浓度([Ca~(2+)]_0)的作用相比较时，异丙肾上腺素增加的肌原纤维的钙敏感性比改变[Ca~(2+)]_0时的峰值信号高，这表明刺激β-肾上腺素受体产生的环磷酸腺苷降低了肌原纤维对钙的敏感性。卡巴胆碱对基础肌力和环磷酸腺苷水平无显著影响，但可降低福司可林、MDL 17,043或异丙肾上腺素引起的环磷酸腺苷水平升高。它以浓度依赖的方式拮抗这些药物引起的峰信号和力的增加。当卡巴胆碱先于异丙肾上腺素给药，并在卡巴胆碱存在下测定异丙肾上腺素的量效曲线时，卡巴胆碱不改变兔乳头状肌力峰信号的关系。在Forsklin、MDL 17,043和异丙肾上腺素的正性变力作用诱导过程中，卡巴胆碱以浓度依赖的方式减弱犬心室肌小梁的肌力而不是峰信号。因此，在卡巴胆碱诱导的抑制过程中，力与峰信号的关系下移，表明卡巴胆碱进一步降低了肌原纤维对钙的敏感性。卡巴胆碱的这种作用似乎是环腺苷酸介导的正性变力作用所特有的，因为α肾上腺素受体介导的(环腺苷非依赖性)作用不受卡巴胆碱影响。这一机制可能对哺乳动物心肌的“强烈拮抗”起重要作用。
The relation of changes in intracellular calcium transients and force of isometric contractions in response to an elevation or reduction of cyclic AMP levels was investigated in isolated dog ventricular trabeculae and rabbit papillary muscles, in which multiple superficial cells have been microinjected with the calcium sensitive bioluminescent protein aequorin. Forskolin, MDL 17,043 and isoprenaline elevated the tissue cyclic AMP level, increased consistently the peak aequorin signals and force, and abbreviated the duration of both signals in a concentration-dependent manner. When the effect of isoprenaline was compared with that of alteration of extracellular calcium concentration ([Ca2+]0), the increase in force by isoprenaline was associated with higher peak aequorin signals than that by alteration of [Ca2+]0for a given increase in force, indicating the decrease in calcium sensitivity of myofibrils by cyclic AMP generated byβ-adrenoceptor stimulation. Carbachol, which did not affect significantly the basal force and cyclic AMP levels, lowered the cyclic AMP levels elevated previously by forskolin, MDL 17,043 or isoprenaline in the isolated dog ventricular trabeculae. It antagonized the increase in peak aequorin signals and force caused by these agents in a concentration-dependent manner. When carbachol had been administered prior to isoprenaline and the concentration-response curve for isoprenaline was determined in the presence of carbachol, the relation of force peak aequorin signals was not modified by carbachol in the rabbit papillary muscle. Carbachol, when administered during induction of the positive inotropic action by forskolin, MDL 17,043 and isoprenaline, decreased the force more than peak aequorin signals in a concentration-dependent manner in the dog ventricular trabeculae. Therefore, the relation of force to peak aequorin signals was shifted downwards during the carbachol-induced inhibition, indicating a further decrease of calcium sensitivity of myofibrils by carbachol. This effect of carbachol appears to be specific to the cyclic AMP-mediated positive inotropic action, since theα-adrenoceptor-mediated (cyclic AMP-independent) action was unaffected by carbachol. This mechanism may play an important role for “accentuated antagonism” in the mammalian ventricular myocardium.
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发表时间：
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影响因子：
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