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A Ras-dependent chloride current activated by adrenocorticotropin in rat adrenal zona glomerulosa cells.

Abstract：

:In the present study, we report that ACTH induces a transient chloride current. The lack of correlation between ACTH-induced cAMP production and amplitude of the Cl- current, as well as the absence of stimulation by forskolin or 8Br-cAMP indicated that the ACTH-induced current was not cAMP-dependent. We explored the possibility that one or several elements of the Ras/Raf MAPK cascade were involved. Indeed, we found that ACTH at 10(-10) M induced activation of Ras. Inhibition of the current by QEHA peptide, a Gbetagamma sequestrant, demonstrated that Gbetagamma subunits transduced the message. Blockage of the Ras activation using an inhibitor of farnesyl transferase (BZA-5B) or the monoclonal antibody H-Ras(259) abrogated the current. Moreover, the addition of Ras-GTPyS in the pipette medium gave rise to the Cl- current. Treatment of the cells with BZA decreased the aldosterone secretion induced by 10(-10) M ACTH but not that induced by 10(-8) M ACTH, confirming the involvement of Ras in steroid secretion. We conclude that ACTH triggers a Cl- current through the activation of the Ras protein by Gbetagamma subunits. This current, activated at physiological ACTH concentrations (1 to 100 pM) where cAMP production is very low, could play a significant role in aldosterone production.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Chorvátová A,Gendron L,Bilodeau L,Gallo-Payet N,Payet MD

doi

10.1210/endo.141.2.7328

subject

Has Abstract

pub_date

2000-02-01 00:00:00

pages

684-92

issue

2

eissn

0013-7227

issn

1945-7170

journal_volume

141

pub_type

杂志文章

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