ALPHA-1-ADRENOCEPTOR SUBTYPES LINKED TO DIFFERENT MECHANISMS FOR INCREASING INTRACELLULAR CA-2+ IN SMOOTH-MUSCLE
ALPHA-1-ADRENOCEPTOR SUBTYPES LINKED TO DIFFERENT MECHANISMS FOR INCREASING INTRACELLULAR CA-2+ IN SMOOTH-MUSCLE
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DOI：
10.1038/329333a0
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发表时间：
1987-09-24
期刊：
影响因子：
64.8
通讯作者：
MINNEMAN, KP
中科院分区：
文献类型：
--
作者：
HAN, C;ABEL, PW;MINNEMAN, KP
受体介导的细胞内Ca 2+水平的增加可以由细胞内细胞器的释放和/或细胞外液的流入引起。交感神经释放的去甲肾上腺素（NA）作用于α1-肾上腺素受体，增加胞浆Ca 2+，促进平滑肌收缩1。在许多细胞中，α1-肾上腺素受体的激活导致肌醇1，4，5-三磷酸的形成，其促进细胞内储存的Ca 2+释放2，3。受体激活打开细胞表面Ca 2+通道的机制尚不清楚，尽管在某些情况下，可能是继发于磷酸肌醇的形成4，5或储存的细胞内Ca 2+的释放（参考文献3）。然而，最近发现α1-肾上腺素能受体在不同组织中具有不同的药理学特性6 -9，并提出不同的α1-肾上腺素能受体亚型可能控制细胞内Ca 2+的动员和细胞外Ca 2+流入的门控7，9，10-12。我们在此报道了两种α1肾上腺素受体亚型的证据，它们通过不同的分子机制引起收缩反应。一种亚型刺激磷酸肌醇（InsP）形成并引起不依赖于细胞外Ca 2+的收缩，另一种亚型不刺激磷酸肌醇形成并引起需要细胞外Ca 2+通过二氢吡啶敏感性通道流入的收缩。这些结果表明，神经递质和激素可以控制Ca 2+释放从细胞内存储和流入通过电压门控膜通道通过不同的受体亚型。
Receptor-mediated increases in intracellular Ca2+levels can be caused by release from intracellular organelles and/or influx from the extracellular fluid. Noradrenaline (NA) released from sympathetic nerves acts on α1-adrenoceptors to increase cytosolic Ca2+and promote smooth muscle contraction1. In many cells activation of α1-adrenoceptors causes formation of inositol 1,4,5-trisphosphate which promotes Ca2+release from intracellular stores2,3. The mechanism by which receptor activation opens cell surface Ca2+channels is not known, although in some cases it may be secondary to formation of inositol phosphates4,5or release of stored intracellular Ca2+(ref. 3). However α1-adrenoceptors have recently been shown to have different pharmacological properties in different tissues6–9, and it has been proposed that different α1-adrenoceptor subtypes may control mobilization of intracellular Ca2+and gating of extracellular Ca2+influx7,9,10–12. We here report evidence for two subtypes of α1-adrenoceptors which cause contractile responses through different molecular mechanisms. One subtype stimulates inositol phosphate (InsP) formation and causes contractions which are independent of extracellular Ca2+, and the other does not stimulate inositol phosphate formation and causes contractions which require the influx of extracellular Ca2+through dihydropyridine-sensitive channels. These results suggest that neurotransmitters and hormones may control Ca2+release from intracellular stores and influx through voltage-gated membrane channels through distinct receptor subtypes.