ArticleThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology2021
Melatonin modulates nitric oxide-regulated WNK-SPAK/OSR1-NKCC1 signaling in dorsal raphe nucleus of rats.
Article in The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.The Biochemical journal · 2026Review
- Exogenous Melatonin as a Sleep-promoting Agent beyond its Chronobiotic Properties: A Scoping Review of its Effects on Key Sleep-wake Neurotransmitters.Current neuropharmacology · 2026Article
- The Informational Blackout chronic pain and fatigue as rational outputs of a brain operating on degraded biological signals.Frontiers in pain research (Lausanne, Switzerland) · 2026Article
- The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- Sex-specific modulation of the medial prefrontal cortex by glutamatergic median raphe neurons.Science advances · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin's wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride cotransporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.
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