Identification of multiple phosphoinositide-linked receptors on human SK-N-MC neuroepithelioma cells.
Identification of multiple phosphoinositide-linked receptors on human SK-N-MC neuroepithelioma cells.
复制标题
人 SK-N-MC 神经上皮瘤细胞上多个磷酸肌醇连接受体的鉴定。
DOI：
10.1111/j.1471-4159.1991.tb06357.x
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发表时间：
1991
影响因子：
4.7
通讯作者：
Landon,RE
中科院分区：
文献类型：
--
作者：
Fisher,SK;Landon,RE
:The biochemical and pharmacological characteristics of receptor‐stimulated phosphoinositide (PPI) hydrolysis in human SK‐N‐MC neuroepithelioma cells have been examined. Of 11 ligands tested, the addition of four, i.e., nor‐epinephrine, oxotremorine‐M, endothelin‐1, and ATP, each resulted in an increased release (three‐to eightfold) of inositol phosphates from [3H]inositol‐prelabeled cells. Agonist‐stimulated PPI turnover was sustained for at least 30 min and required the addition of Ca2+for full effect. An increased release of inositol phosphates could also be elicited by the addition of the Ca2+ionophore, ionomycin. All four agonists enhanced the release of radiolabeled inositol mono‐and bis‐phosphates, inositol 1,3,4‐trisphosphate, and inositol tetra‐kisphosphate. Increases in inositol 1,4,5‐trisphosphate were smaller and only consistently observed in the presence of norepinephrine or oxotremorine‐M. Norepinephrine‐stim‐ulated PPI turnover was potently inhibited by prazosin, WB‐4101, and 5‐methylurapidil (K1, < 2.5 nM), but was relatively insensitive to chloroethylclonidine pretreatment. This pharmacological profile is consistent with the involvement of an α1A‐receptor subtype. The presence of an M1muscannic cholinergic receptor is also indicated, because pirenzepine blocked oxotremorine‐M‐stimulated inositol phosphate release (K1= 35 nM) with a 30‐fold greater potency than the M2‐selective antagonist, AF‐DX 116. Of the three endothelins tested, only the addition of endothelin‐1 and endothelin‐2 promoted PPI hydrolysis, whereas endothelin‐3 was essentially inactive. A P2nucleotide receptor of broad agonist specificity is also present on these cells and activates PPI turnover in the absence of a generalized increase in plasma membrane permeability. These results indicate that SK‐N‐MC cells express at least four PPI‐linked receptors. Because the functional coupling of three of these receptors, i.e., α1A‐adrenergic, endothelin, and P2nucleotide, has not been extensively characterized previously in neural tissues, the SK‐N‐MC cell line may provide a useful model system for studies of these receptors and their regulation.
