Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes
Arachidonic acid (AA) is generated in the anterior pituitary gland upon stimulation by the ACTH secretagogue, CRH. Using the patch clamp technique, we examined the action of AA on the excitability of single pituitary corticotropes obtained from a transgenic mouse strain that expresses the enhanced g...
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todo:paper_00137227_v152_n5_p1901_Lee2023-10-03T14:11:22Z Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes Lee, A.K. Smart, J.L. Rubinstein, M. Low, M.J. Tse, A. 8 (4 chlorophenylthio) cyclic AMP adenylate cyclase arachidonic acid chlorpromazine corticotropin releasing factor diphenylbutylpiperidine derivative enhanced green fluorescent protein fluoxetine potassium channel potassium ion twik related potassium channel 1 unclassified drug acidification ACTH secreting cell animal cell article controlled study fatty acid metabolism hyperpolarization membrane depolarization mouse nonhuman potassium current priority journal protein expression voltage clamp Animals Arachidonic Acid Cells, Cultured Chlorpromazine Corticotrophs Corticotropin-Releasing Hormone Cyclic AMP Fluoxetine Green Fluorescent Proteins Hydrogen-Ion Concentration Membrane Potentials Mice Mice, Transgenic Neuroprotective Agents Patch-Clamp Techniques Potassium Channels, Tandem Pore Domain Thionucleotides Arachidonic acid (AA) is generated in the anterior pituitary gland upon stimulation by the ACTH secretagogue, CRH. Using the patch clamp technique, we examined the action of AA on the excitability of single pituitary corticotropes obtained from a transgenic mouse strain that expresses the enhanced green fluorescent protein driven by the proopiomelanocortin promoter. CRH evoked depolarization, but AA caused hyperpolarization. Under voltage clamp condition, AA caused a rapid inhibition of the delayed rectifier K+ current and then increased a background K+ current. Inhibition of AA metabolism did not prevent the activation of the K+ current by AA, suggesting a direct action of AA. The sensitivity of the AA-activated K+ current to fluoxetine, chlorpromazine, extracellular acidification, diphenylbutylpiperidine antipsychotics, and the membrane permeable cAMP analog [8-(4-chlorophenylthio)-cAMP] suggest that the current is mediated via TWIK-related K+ channel (TREK)-1 channels. Activation of the CRH receptors that are coupled to the adenylate cyclase pathway suppressed the activation of TREK-1 current by AA and reversed the AA-mediated hyperpolarization. Intracellular acidification (pH 7.0) increased the basal amplitude of TREK-1 current and resulted in hyperpolarizaton. CRH suppressed the basal TREK-1 current in cells with intracellular acidification and caused depolarization. Our finding indicates that TREK-1 channels are important in setting the resting potential in corticotropes. The opposing actions of CRH and AA on the excitability of corticotropes raise the possibility that AA may act as a negative feedback regulator to reduce the stimulatory action of CRH and thus prevent excessive ACTH release during chronic stress. Copyright © 2011 by The Endocrine Society. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00137227_v152_n5_p1901_Lee |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
8 (4 chlorophenylthio) cyclic AMP adenylate cyclase arachidonic acid chlorpromazine corticotropin releasing factor diphenylbutylpiperidine derivative enhanced green fluorescent protein fluoxetine potassium channel potassium ion twik related potassium channel 1 unclassified drug acidification ACTH secreting cell animal cell article controlled study fatty acid metabolism hyperpolarization membrane depolarization mouse nonhuman potassium current priority journal protein expression voltage clamp Animals Arachidonic Acid Cells, Cultured Chlorpromazine Corticotrophs Corticotropin-Releasing Hormone Cyclic AMP Fluoxetine Green Fluorescent Proteins Hydrogen-Ion Concentration Membrane Potentials Mice Mice, Transgenic Neuroprotective Agents Patch-Clamp Techniques Potassium Channels, Tandem Pore Domain Thionucleotides |
| spellingShingle |
8 (4 chlorophenylthio) cyclic AMP adenylate cyclase arachidonic acid chlorpromazine corticotropin releasing factor diphenylbutylpiperidine derivative enhanced green fluorescent protein fluoxetine potassium channel potassium ion twik related potassium channel 1 unclassified drug acidification ACTH secreting cell animal cell article controlled study fatty acid metabolism hyperpolarization membrane depolarization mouse nonhuman potassium current priority journal protein expression voltage clamp Animals Arachidonic Acid Cells, Cultured Chlorpromazine Corticotrophs Corticotropin-Releasing Hormone Cyclic AMP Fluoxetine Green Fluorescent Proteins Hydrogen-Ion Concentration Membrane Potentials Mice Mice, Transgenic Neuroprotective Agents Patch-Clamp Techniques Potassium Channels, Tandem Pore Domain Thionucleotides Lee, A.K. Smart, J.L. Rubinstein, M. Low, M.J. Tse, A. Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes |
| topic_facet |
8 (4 chlorophenylthio) cyclic AMP adenylate cyclase arachidonic acid chlorpromazine corticotropin releasing factor diphenylbutylpiperidine derivative enhanced green fluorescent protein fluoxetine potassium channel potassium ion twik related potassium channel 1 unclassified drug acidification ACTH secreting cell animal cell article controlled study fatty acid metabolism hyperpolarization membrane depolarization mouse nonhuman potassium current priority journal protein expression voltage clamp Animals Arachidonic Acid Cells, Cultured Chlorpromazine Corticotrophs Corticotropin-Releasing Hormone Cyclic AMP Fluoxetine Green Fluorescent Proteins Hydrogen-Ion Concentration Membrane Potentials Mice Mice, Transgenic Neuroprotective Agents Patch-Clamp Techniques Potassium Channels, Tandem Pore Domain Thionucleotides |
| description |
Arachidonic acid (AA) is generated in the anterior pituitary gland upon stimulation by the ACTH secretagogue, CRH. Using the patch clamp technique, we examined the action of AA on the excitability of single pituitary corticotropes obtained from a transgenic mouse strain that expresses the enhanced green fluorescent protein driven by the proopiomelanocortin promoter. CRH evoked depolarization, but AA caused hyperpolarization. Under voltage clamp condition, AA caused a rapid inhibition of the delayed rectifier K+ current and then increased a background K+ current. Inhibition of AA metabolism did not prevent the activation of the K+ current by AA, suggesting a direct action of AA. The sensitivity of the AA-activated K+ current to fluoxetine, chlorpromazine, extracellular acidification, diphenylbutylpiperidine antipsychotics, and the membrane permeable cAMP analog [8-(4-chlorophenylthio)-cAMP] suggest that the current is mediated via TWIK-related K+ channel (TREK)-1 channels. Activation of the CRH receptors that are coupled to the adenylate cyclase pathway suppressed the activation of TREK-1 current by AA and reversed the AA-mediated hyperpolarization. Intracellular acidification (pH 7.0) increased the basal amplitude of TREK-1 current and resulted in hyperpolarizaton. CRH suppressed the basal TREK-1 current in cells with intracellular acidification and caused depolarization. Our finding indicates that TREK-1 channels are important in setting the resting potential in corticotropes. The opposing actions of CRH and AA on the excitability of corticotropes raise the possibility that AA may act as a negative feedback regulator to reduce the stimulatory action of CRH and thus prevent excessive ACTH release during chronic stress. Copyright © 2011 by The Endocrine Society. |
| format |
JOUR |
| author |
Lee, A.K. Smart, J.L. Rubinstein, M. Low, M.J. Tse, A. |
| author_facet |
Lee, A.K. Smart, J.L. Rubinstein, M. Low, M.J. Tse, A. |
| author_sort |
Lee, A.K. |
| title |
Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes |
| title_short |
Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes |
| title_full |
Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes |
| title_fullStr |
Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes |
| title_full_unstemmed |
Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes |
| title_sort |
reciprocal regulation of trek-1 channels by arachidonic acid and crh in mouse corticotropes |
| url |
http://hdl.handle.net/20.500.12110/paper_00137227_v152_n5_p1901_Lee |
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1807321272456052736 |