GHRH activates a nonselective cation current in human GH-secreting adenoma cells.

GHRH activates a nonselective cation current in human GH-secreting adenoma cells.
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GHRH 激活人类 GH 分泌腺瘤细胞中的非选择性阳离子电流。

DOI:
10.1152/ajpendo.1996.270.6.e1050
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发表时间:
1996
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
N. Yamashita
N. Yamashita
中科院分区:
--
文献类型:
--
作者:
K. Takano;T. Takei;A. Teramoto;N. Yamashita

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用穿孔全细胞钳技术分析人生长激素释放激素(GHRH)对人生长激素(GH)腺瘤细胞的电生理反应。HGHRH通过增加Na+电导使膜去极化。HGHRH诱导电流的反转电位为-20~0 mV。该通道对Na+、Li+、K+有通透性,对TMA+无通透性。这些性质与非选择性阳离子通道的性质是一致的。8-溴腺苷3‘,5’-环一磷酸和Forsklin也激活了非选择性阳离子电流,而蛋白激酶A抑制剂、(R)-对环腺苷3‘,5’-环一磷酸和N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoleinsulfonamide,以及PKA抑制肽PKI-(5-24)均能抑制hGHRH诱导电流的激活,表明hGHRH诱导电流是由PKA激活的。霍乱毒素预处理消除了hGHRH诱导的电流,提示Gs参与了该电流的激活。该电流在冈田酸处理后不可逆,提示hGHRH诱导电流的恢复是由丝氨酸/苏氨酸蛋白磷酸酶介导的。在无钠介质中,GHRH诱导的GH分泌受到抑制,提示非选择性阳离子电流在hGHRH诱导的GH分泌中的重要性。在人类GH分泌的非腺瘤细胞中,hGHRH增加Na+电导,就像在GH分泌的腺瘤细胞中一样。
Electrophysiological responses induced by human (h) growth hormone-releasing hormone (GHRH) were analyzed using the perforated whole cell clamp technique in human growth hormone (GH)-secreting adenoma cells. Application of hGHRH depolarized the membrane by increasing Na+ conductance. The reversal potential of the hGHRH-induced current was -20 to 0 mV. The channel was permeable to Na+, Li+ and K+ but not to TMA+. These properties were compatible with those of nonselective cation channels. Similar nonselective cation current was activated by 8-bromoadenosine 3',5'-cyclic monophosphate and forskolin, and the activation of the hGHRH-induced current was inhibited by protein kinase A (PKA) inhibitors, (R)-p-adenosine 3',5'-cyclic monophosphate and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoleinsulfonamide, and PKA inhibitor peptide PKI-(5-24), indicating that hGHRH-induced current was activated by PKA. Cholera toxin pretreatment eliminated the hGHRH-induced current, suggesting that Gs is involved in the activation of this current. This current became irreversible when the cells were pretreated with okadaic acid, suggesting that the recovery of the hGHRH-induced current was mediated by a serine/threonine protein phosphatase. GHRH-induced GH secretion was inhibited in Na+-free medium, suggesting the importance of the nonselective cation current on hGHRH-induced GH secretion. In human GH-secreting nonadenoma cells, hGHRH increased Na+ conductance, as was the case in GH-secreting adenoma cells.
DOI: 10.1016/0006-291x(89)92189-x
发表时间: 1989-03-31
影响因子: 3.1
作者:
ISHIHARA, H;MARTIN, BL;HARTSHORNE, DJ
通讯作者: HARTSHORNE, DJ
DOI: 10.1073/pnas.77.12.7492
发表时间: 1980-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
CASTELLUCCI, VF;KANDEL, ER;GREENGARD, P
通讯作者: GREENGARD, P