ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Osmoregulation requires brain expression of the renal Na-K-2Cl cotransporter NKCC2.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- The NKCC1 Antagonist Bumetanide, Administered After Prenatal Alcohol Exposure, Mitigates Ethanol-Induced Aberrance in Tangential Migration of GABAergic Interneurons in Mouse Medial Prefrontal Cortex.Alcohol, clinical & experimental research · 2026Article
- Sex differences in central salt sensing in the human brain.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Diuretics: a review of the pharmacology and effects on glucose homeostasis.Frontiers in pharmacology · 2025Review
- Acute hypernatremia increases functional connectivity of NaCl sensing regions in the human brain: An fMRI pilot study.Autonomic neuroscience : basic & clinical · 2024Article
- Efficacy of bumetanide tablets combined with valsartan in the treatment of elderly patients with chronic glomerulonephritis and its effects on renal function and hemodynamics.American journal of translational research · 2023Article
- Dietary sodium and health: How much is too much for those with orthostatic disorders?Autonomic neuroscience : basic & clinical · 2022Review
- Osmoregulation and the Hypothalamic Supraoptic Nucleus: From Genes to Functions.Frontiers in physiology · 2022Review
- Cardiovascular Neuroendocrinology: Emerging Role for Neurohypophyseal Hormones in Pathophysiology.Endocrinology · 2021Review
- High glucose-induced effects on NaAmerican journal of physiology. Cell physiology · 2021Article
- Role of angiotensin II in chronic intermittent hypoxia-induced hypertension and cognitive decline.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Review
- Molecular characteristics and physiological roles of NaJournal of cellular physiology · 2021Review
- Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for the Therapy of Stroke.International journal of molecular sciences · 2021Review
- Advances in the neurophysiology of magnocellular neuroendocrine cells.Journal of neuroendocrinology · 2020Review
- Impaired glucose tolerance, glucagon, and insulin responses in mice lacking the loop diuretic-sensitiveAmerican journal of physiology. Cell physiology · 2019Article
- The WNK-SPAK/OSR1 Kinases and the Cation-Chloride Cotransporters as Therapeutic Targets for Neurological Diseases.Aging and disease · 2019Review
- The transcriptome of the rat subfornical organ is altered in response to early postnatal overnutrition.IBRO reports · 2018Article
- The effects of aging on biosynthetic processes in the rat hypothalamic osmoregulatory neuroendocrine system.Neurobiology of aging · 2018Article
- Chloride Homeostasis in Neurons With Special Emphasis on the Olivocerebellar System: Differential Roles for Transporters and Channels.Frontiers in cellular neuroscience · 2018Review
- NaCl and osmolarity produce different responses in organum vasculosum of the lamina terminalis neurons, sympathetic nerve activity and blood pressure.The Journal of physiology · 2017Article
- Hypothalamic Signaling in Body Fluid Homeostasis and Hypertension.Current hypertension reports · 2017Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 5 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.