Projects per year
Abstract
The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution-rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats.
Original language | English |
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Pages (from-to) | 5144-5155 |
Number of pages | 12 |
Journal | Journal of Neuroscience |
Volume | 35 |
Issue number | 13 |
DOIs | |
Publication status | Published - 1 Apr 2015 |
Keywords
- Fluid balance
- GABA
- Hypothalamo-neurohypophyseal system
- Loop diuretics
- Slc12a1/NKCC2
Fingerprint
Dive into the research topics of 'Osmoregulation Requires Brain Expression of the Renal Na-K-2Cl Cotransporter NKCC2'. Together they form a unique fingerprint.Projects
- 2 Finished
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Bilateral BBSRC-FAPESP: Behavioural and neuroendocrine mechanisms regulating hydromineral homeostasis - a lifelong perspective
10/01/13 → 10/05/16
Project: Research
Equipment
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Wolfson Bioimaging Facility
Mark Jepson (Manager)
Faculty of Life SciencesFacility/equipment: Facility
Profiles
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Professor David Murphy
- Bristol Medical School (THS) - Professor of Experimental Medicine
- Laboratories for Integrative Neuroscience and Endocrinology
- Molecular Neuroendocrinology Research Group
- Bristol Neuroscience
Person: Academic , Member, Group lead