Evidence for cAMP-independent bTREK-1 inhibition by ACTH and NPS-ACTH in adrenocortical cells

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• 作者：John J. Enyeart  ; ;   ; ^{enyeart.1@osu.edu} ; Haiyan Liu¹ ; Judith A. Enyeart
• 关键词：Adrenal ; ACTH ; TREK-1 K⁺ channel ; cAMP
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2012
• 出版时间：2 January 2012
• 年：2012
• 卷：348
• 期：1
• 页码：305-312
• 全文大小：534 K

文摘

Bovine adrenal zona fasciculata (AZF) cells express bTREK-1 K⁺ channels that are inhibited by ACTH through cAMP-dependent pathways. In whole cell patch clamp recordings from AZF cells, we found that ACTH may also inhibit bTREK-1 by a cAMP-independent mechanism. When the potent adenylyl cyclase (AC) antagonist 2,5-dideoxyadenosine-3?triphosphate (2,5-dd-3?ATP) was applied intracellularly through the patch pipette, bTREK-1 inhibition by the AC activator forskolin was blocked. In contrast, bTREK-1 inhibition by ACTH was unaltered. The selective G_S¦Á antagonist NF449 also failed to blunt bTREK-1 inhibition by ACTH. At concentrations that produce little measurable increase in cAMP in bovine AZF cells, the O-nitrophenyl, sulfenyl-derivative of ACTH (NPS-ACTH) also inhibited bTREK-1 almost completely. Accordingly, 2,5-dd-3?ATP at concentrations more than 1000¡Á its reported IC₅₀ did not block bTREK-1 inhibition by NPS-ACTH. These results indicate that ACTH and NPS-ACTH can inhibit native bTREK-1 K⁺ channels in AZF cells by a mechanism that does not involve activation of AC.