Developmental changes in β‐adrenoceptors, muscarinic cholinoceptors and Ca2+ channels in rat ventricular muscles
Developmental changes in β‐adrenoceptors, muscarinic cholinoceptors and Ca2+ channels in rat ventricular muscles
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大鼠心室肌β-肾上腺素受体、毒蕈碱胆碱受体和Ca2+通道的发育变化
DOI：
--
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发表时间：
1990
影响因子：
7.3
通讯作者：
N. Sperelakis
中科院分区：
文献类型：
--
作者：
M. Kojima;T. Ishima;N. Taniguchi;K. Kimura;H. Sada;N. Sperelakis
1 为了解释先前关于 β-肾上腺素能和毒蕈碱胆碱能相互作用对心脏 Ca2+ 电流的个体发育的电生理学数据，对发育中的大鼠心肌中 β-肾上腺素能受体、毒蕈碱胆碱能受体和 Ca2+ 通道的个体发育进行了生化研究：16-20 天大的胎儿、0-20 天大的新生儿和2-3个月大的成人。 2 分别使用特定放射性配体 [3H]-二氢阿普洛尔 (DHA)、[3H]-苯甲酸奎宁环酯 (QNB) 和 [3H]-尼群地平 (NTD) 测定心脏 β-肾上腺素受体、毒蕈碱胆碱受体和 Ca2+ 通道的发育变化。 3 [3H]-DHA 结合的 Bmax 值（fmol mg−1 组织）在妊娠后第 20 天开始增加，在新生儿第 6 天几乎达到最高水平，直到新生儿第 20 天几乎保持相同水平，然后略有下降至成人水平。 4 [3H]-QNB 结合的 Bmax 值（fmol mg−1 组织）在妊娠后第 16 天开始增加，在新生儿第 0 天几乎达到最高水平，直到新生儿第 15 天几乎保持恒定，然后下降到成人水平。 5 [3H]-NTD 结合的 Bmax 值（fmol mg−1 组织）在妊娠后第 18 天到新生儿第 15 天之间随着年龄的增长而增加，直到新生儿第 20 天几乎保持恒定，然后下降到成人水平。 6 [3H]-DHA、[3H]-QNB 和 [3H]-NTD 结合的 Kd 值在所检查的发育期间几乎保持恒定。 7 异丙肾上腺素（Iso）从妊娠后第18天开始增加慢动作电位（APs），并在出生后约2周达到成人水平；该发育时间过程与 Ca2+ 通道类似。 β-肾上腺素受体的数量也在出生前几天开始增加，但比慢速 AP 或 Ca2+ 通道的数量早约一周达到峰值。 8 乙酰胆碱 (ACh) 几乎完全消除了从妊娠后第 18 天到新生儿第 20 天观察到的 Iso 诱导的增加；乙酰胆碱效应的这一发育时间进程与毒蕈碱胆碱感受器的数量在妊娠后第 16 天开始增加并在出生当天达到峰值的发现一致。 9 先前的电生理学和目前的生化研究结果强烈表明，当 β-肾上腺素受体和 Ca2+ 电流之间的耦合开始在发育中的大鼠心脏中发挥作用时，毒蕈碱胆碱受体和 Ca2+ 电流之间的功能耦合就已经建立。
1 In an attempt to explain the previous electrophysiological data on the ontogeny of β‐adrenergic and muscarinic cholinergic interactions on cardiac Ca2+ current, biochemical studies were performed on the ontogeny of β‐adrenoceptors, muscarinic cholinoceptors and Ca2+ channels in cardiac muscle of developing rats: 16–20 days old foetuses, 0–20 days old neonates, and 2–3 months old adults. 2 Developmental changes in cardiac β‐adrenoceptors, muscarinic cholinoceptors, and Ca2+ channels were determined with the use of specific radioligands, [3H]‐dihydroalprenolol (DHA), [3H]‐quinuclidinyl benzilate (QNB), and [3H]‐nitrendipine (NTD), respectively. 3 The Bmax value (fmol mg−1 tissue) for [3H]‐DHA binding started to increase on post‐gestation day 20, reached almost its maximum level on neonatal day 6, kept almost the same level until neonatal day 20, and then decreased slightly to its adult level. 4 The Bmax value (fmol mg−1 tissue) for [3H]‐QNB binding started to increase on post‐gestation day 16, reached almost its maximum level on neonatal day 0, remained almost constant until neonatal day 15, and then decreased to its adult level. 5 The Bmax value (fmol mg−1 tissue) for [3H]‐NTD binding increased with age between post‐gestation day 18 and neonatal day 15, stayed almost constant until neonatal day 20, and then decreased to its adult level. 6 The Kd values for [3H]‐DHA, [3H]‐QNB, and [3H]‐NTD bindings remained almost constant during the developmental period examined. 7 Isoprenaline (Iso) increased the of slow action potentials (APs) from post‐gestation day 18, and the adult level was reached at about 2 weeks after birth; this developmental time course is similar to that of Ca2+ channels. The number of β‐adrenoceptors also started to increase a few days before birth, but attained its peak about one week earlier than did the of slow APs or the number of Ca2+ channels. 8 Acetylcholine (ACh) almost completely abolished the Iso‐induced increase in observed from post‐gestation day 18 to neonatal day 20; this developmental time course for the ACh effect is consistent with the finding that the number of muscarinic cholinoceptors started to increase on post‐gestation day 16 and reached a peak on the day of birth. 9 Previous electrophysiological and the present biochemical findings strongly suggest that the functional coupling between muscarinic cholinoceptors and Ca2+ current is already established when the coupling between β‐adrenoceptors and Ca2+ current starts to operate in developing rat hearts.
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