An antagonist-insensitive P-2X receptor expressed in epithelia and brain
An antagonist-insensitive P-2X receptor expressed in epithelia and brain
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DOI：
10.1002/j.1460-2075.1996.tb00333.x
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发表时间：
1996-01-02
期刊：
影响因子：
11.4
通讯作者：
Surprenant, A
中科院分区：
文献类型：
--
作者：
Buell, G;Lewis, C;Surprenant, A
克隆了一个编码新的ATP门控离子通道（P2X（4）受体）的cDNA。ATP在用P2X（4）受体转染的HEK293细胞中诱导阳离子电流。然而，该电流几乎完全不敏感的拮抗剂有效的其他P-2X受体。对这些拮抗剂中的两种（磷酸吡哆醛-6-偶氮苯基-2 '，4'-二磺酸和5-磷酸吡哆醛）的敏感性通过赖氨酸取代Glu 249而恢复，这发生在P2X（1）和P2X（2）受体的等同位置。P2X（4）RNA通过原位杂交在脑、周围神经节和包括唾液腺的浆膜细胞在内的上皮中被发现。大鼠下颌下腺细胞的记录显示ATP诱导的电流也对拮抗剂不敏感。这些结果确定了P-2X受体家族的另一个成员，并确定了参与拮抗剂结合的氨基酸残基，它们还在P-2X受体处引入了ATP应答的新表型-对目前已知的拮抗剂不敏感。
A cDNA was cloned which encodes a new ATP-gated ion channel (P2X(4) receptor). ATP induces a cationic current in HEK293 cells transfected with the P2X(4) receptor. However, the current is almost completely insensitive to antagonists effective at other P-2X receptors. Sensitivity to two of these antagonists (pyridosalphosphate-6-azophenyl-2',4'-disulfonic acid and pyridoxal 5-phosphate) is restored by replacement of Glu249 by lysine, which occurs at the equivalent position in P2X(1) and P2X(2) receptors. P2X(4) RNA is found by in situ hybridization in the brain, peripheral ganglia and epithelia including serosal cells of salivary glands, Recordings from rat submandibular gland cells showed ATP-induced currents that are also insensitive to antagonists, These results define a further member of P-2X receptor family, and they identify an amino acid residue involved in antagonist binding, They also introduce a new phenotype for ATP responses at P-2X receptors-insensitivity to currently known antagonists.