STIMULATION OF HYPERTROPHY OF CULTURED NEONATAL RAT-HEART CELLS THROUGH AN ALPHA-1-ADRENERGIC RECEPTOR AND INDUCTION OF BEATING THROUGH AN ALPHA-1-ADRENERGIC AND BETA-1-ADRENERGIC RECEPTOR INTERACTION - EVIDENCE FOR INDEPENDENT REGULATION OF GROWTH AND BEATIN
STIMULATION OF HYPERTROPHY OF CULTURED NEONATAL RAT-HEART CELLS THROUGH AN ALPHA-1-ADRENERGIC RECEPTOR AND INDUCTION OF BEATING THROUGH AN ALPHA-1-ADRENERGIC AND BETA-1-ADRENERGIC RECEPTOR INTERACTION - EVIDENCE FOR INDEPENDENT REGULATION OF GROWTH AND BEATIN
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DOI：
10.1161/01.res.56.6.884
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发表时间：
1985-01-01
影响因子：
20.1
通讯作者：
SIMPSON, P
中科院分区：
文献类型：
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作者：
SIMPSON, P
儿茶酚胺可能是将循环需求增加与心肌肥大联系起来的分子信号之一，之前发现去甲肾上腺素通过α1-肾上腺素能受体刺激培养的新生大鼠心肌细胞肥大。由于儿茶酚胺对收缩性的刺激被认为是在β-肾上腺素能控制下，因此研究了这些培养的心脏细胞是否具有分别通过α-和β-肾上腺素能受体调节生长和收缩性的双重途径。研究了肾上腺素能药物对无血清培养物中肌细胞肥大和跳动的影响。肥大被定义为肌细胞表面积和细胞蛋白质含量的增加，通过放射性同位素方法测量，并通过肉眼检查变时活性。去甲肾上腺素和肾上腺素是肥大和搏动的等效刺激剂，使细胞蛋白质和面积增加1.5至2倍，搏动细胞的比例从5%或更少增加到95%。最大反应发生在暴露后 24-48 小时，EC50 为 20-200 nM。使用其他激动剂（去氧肾上腺素、甲氧明、可乐定、异丙肾上腺素、多巴胺）和拮抗剂（哌唑嗪、特拉唑嗪、育亨宾、普萘洛尔、倍他洛尔、ICI 118,551 [erythro-DL-1-(7-methylmidan-4-yloxy)-3-isopropaminobutan-2-ol]）的研究表明，肥大是通过α1-肾上腺素能受体，而跳动的诱导需要α1-和β1-受体激活。单独通过α-刺激产生具有最小搏动的肥大细胞。相反，在放线菌酮存在下抑制蛋白质合成的α-加β-刺激导致最大程度的搏动但没有肥大。生长和跳动显然可以通过不同的细胞途径独立调节。
Catecholamines may be one of the molecular signals linking increased circulatory demand to myocardial hypertrophy, and it was found previously that norepinephrine stimulates hypertrophy of cultured neonatal rat heart muscle cells through an .alpha.1-adrenergic receptor. Since catecholamine stimulation of contractility is believed to be under .beta.-adrenergic control, whether these cultured heart cells had dual pathways regulating growth and contractility through .alpha.- and .beta.-adrenergic receptors, respectively, was investigated. The effect of adrenergic agents on hypertrophy and beating of myocytes in serum-free cultures was examined. Hypertrophy was defined as an increase in myocyte surface area and in cell protein content, measured by a radioisotopic method, and chronotropic activity was examined visually. Norepinephrine and epinephrine were equipotent stimulants of hypertrophy and beating, increasing cell protein and area 1.5- to 2-fold, and the proportion of beating cells from 5% or less to 95%. Response maxima occurred 24-48 h after exposure, and EC50 were 20-200 nM. Studies with other agonists (phenylephrine, methoxamine, clonidine, isoproterenol, dopamine) and antagonists (prazosin, terazosin, yohimbine, propranolol, betaxolol, ICI 118,551 [erythro-DL-1-(7-methylmidan-4-yloxy)-3-isopropylaminobutan-2-ol]) indicated that hypertrophy was mediated through an .alpha.1-adrenergic receptor, whereas the induction of beating required both .alpha.1- and .beta.1-receptor activation. Hypertrophied cells with minimal beating were produced by .alpha.-stimulation, alone. In contrast, .alpha.-plus .beta.-stimulation in the presence of cycloheximide to inhibit protein synthesis resulted in maximum beating but no hypertrophy. Growth and beating evidently can be regulated independently through separate cellular pathways.