Expression and functional properties of group I metabotropic glutamate receptors in bovine chromaffin cells

Expression and functional properties of group I metabotropic glutamate receptors in bovine chromaffin cells
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DOI:
10.1002/jnr.10824
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发表时间:
2004-01-15
影响因子:
4.2
通讯作者:
González, MP
González, MP
中科院分区:
医学3区
文献类型:
--
作者:
Arce, C;del Campo, AB;González, MP

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我们证明了在嗜铬细胞中表达的I组代谢型谷氨酸受体(mGluRs)的存在和功能特性。免疫细胞化学技术显示,两个mGluR亚型(mGluR 1 α和mGluR 5)的表达在嗜铬细胞,位于细胞质膜和细胞质周围的核。这些mGluRs对嗜铬细胞中的儿茶酚胺(CA)分泌具有功能活性,因为(1 S,3R)-1-氨基环戊烷-1,3-二羧酸(t-ACPD)和I组mGluRs的特异性激动剂(S)-3,5-二羟基苯甘氨酸(DHPG)都能够以剂量反应方式刺激CA(肾上腺素和去甲肾上腺素)的释放。这些作用被L-(+)-2-氨基-3-膦酰基丙酸(L-AP 3)特异性逆转,L-AP 3是I组代谢型谷氨酸受体的选择性拮抗剂。t-ACPD诱导CA分泌的增加,在存在和不存在细胞外钙,前者的效果伴随着细胞膜去极化。去甲肾上腺素(NA)的释放是更高的细胞外钙的存在下,比在其情况下,而肾上腺素的释放是相同的顺序在这两种条件下。这些结果表明,不同亚型的I组mGIuR存在于去甲肾上腺素能和肾上腺素能细胞中。单细胞荧光成像技术显示不同的t-ACPD诱导的细胞内钙离子增加在不同的嗜铬细胞:在嗜铬细胞中,67%表达功能性代谢型谷氨酸受体和烟碱受体,而其余33%只表达烟碱受体。在没有外部钙的情况下,只有约25%的细胞响应t-ACPD-增加细胞内钙增加肌醇1,4,5-三磷酸(IP 3)浓度和随后的钙动员从细胞内存储,而其余75%增加细胞内钙通过促进Ca 2+流入细胞外介质通过L-和N-,但不是P/Q电压依赖性钙通道。(C)2003 Wiley-Liss,Inc.
We demonstrate the presence and functional properties of Group I metabotropic glutamate receptors (mGluRs) expressed in chromaffin cells. Immunocytochemical techniques revealed that two mGluR subtypes (mGluR1alpha and mGluR5) are expressed in chromaffin cells, located in both the cytoplasmic membrane and the cytosol surrounding the nucleus. These mGluRs are functionally active on catecholamine (CA) secretion in chromaffin cells because both (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) and the specific agonist of Group I mGluRs, (S)-3,5-dihydroxyphenylglycine (DHPG), were able to stimulate the release of CAs (adrenaline and noradrenaline) in a dose-response manner. These effects were specifically reversed by L-(+)-2-amino-3-phosphonopropionic acid (L-AP3), a selective antagonist of the Group I metabotropic glutamate receptors. t-ACPD induced an increase in CA secretion in both the presence and absence of extracellular calcium, the former effect being accompanied by cell membrane depolarization. Noradrenaline (NA) release was higher in the presence of extracellular calcium than in its absence, whereas adrenaline release was of the same order under both conditions. These results indicate that different subtypes of Group I mGIuRs are present in noradrenergic and adrenergic cells. Fluorescence imaging techniques in single cells showed different t-ACPD-induced increases in intracellular calcium in different chromaffin cells: in chromaffin cells, 67% expressed functional metabotropic glutamate receptors and with nicotinic receptors, whereas the remaining 33% expressed only nicotinic receptors. In the absence of external calcium, only about 25% of cells responded to t-ACPD-increased intracellular calcium by increasing inositol 1,4,5-trisphosphate (IP3) concentration and subsequent calcium mobilization from intracellular stores, whereas the remaining 75% increased intracellular calcium by promoting Ca2+ influx from the extracellular medium through L- and N- but not P/Q voltage-dependent calcium channels. (C) 2003 Wiley-Liss,Inc.