Evidence for cAMP-independent bTREK-1 inhibition by ACTH and NPS-ACTH in adrenocortical cells |
| |
Authors: | Enyeart John J Liu Haiyan Enyeart Judith A |
| |
Institution: | Department of Neuroscience, The Ohio State University, College of Medicine and Public Health, Columbus, OH 43210-1239, USA |
| |
Abstract: | 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 GSα 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× 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. |
| |
Keywords: | AZF adrenal zona fasciculatata AZG adrenal zona glomerulosa AC adenylyl cyclase 2 5-dd-3&prime -ATP 2 5-dideoxyadenosine-3&prime -triphosphate FBS fetal bovine sera NPS-ACTH O-nitrophenyl-adrenocorticotropin |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|