ArticleJournal of neurophysiology2015
Spinal 5-HT7 receptors induce phrenic motor facilitation via EPAC-mTORC1 signaling.
Article in Journal of neurophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- Enhanced availability of serotonin increases activation of unfatigued muscle but exacerbates central fatigue during prolonged sustained contractions.The Journal of physiology · 2019Trial
- Sexual dimorphisms in phrenic long-term facilitation following severe acute intermittent hypoxia.Journal of neurophysiology · 2026Article
- Plasticity induced loss of apnea alarm through repeated apneas: A proposed mechanism for respiratory sudden death.Epilepsy & behavior : E&B · 2025Review
- Roflumilast, a phosphodiesterase-4 (PDE4) inhibitor, induces respiratory frequency plasticity that is resistant to inflammation in neonatal rat in vitro preparations.Respiratory physiology & neurobiology · 2025Article
- Daily acute intermittent hypoxia elicits age & sex-dependent changes in molecules regulating phrenic motor plasticity.Experimental neurology · 2025Article
- Can Serotonin 7 Receptors Be a Treatment Target for Noncentral Diseases?The Eurasian journal of medicine · 2023Article
- Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders.International journal of molecular sciences · 2023Review
- BDNF-induced phrenic motor facilitation shifts from PKCθ to ERK dependence with mild systemic inflammation.Journal of neurophysiology · 2023Article
- Therapeutic Potential and Limitation of Serotonin Type 7 Receptor Modulation.International journal of molecular sciences · 2023Review
- Central nervous system effects of 5-HTMolecular medicine (Cambridge, Mass.) · 2022Review
- Epac-2 ameliorates spontaneous colitis in Il-10Journal of cellular and molecular medicine · 2022Article
- The phrenic neuromuscular system.Handbook of clinical neurology · 2022Review
- Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease.Experimental neurology · 2022Review
- Adenosine A2a receptors modulate TrkB receptor-dependent respiratory plasticity in neonatal rats.Respiratory physiology & neurobiology · 2021Article
- How Are Adenosine and Adenosine ABiomedicines · 2021Review
- cAMP signaling through protein kinase A and Epac2 induces substance P release in the rat spinal cord.Neuropharmacology · 2021Article
- Mechanisms of severe acute intermittent hypoxia-induced phrenic long-term facilitation.Journal of neurophysiology · 2021Article
- Serotonin enhances depolarizing spontaneous fluctuations, excitability, and ongoing activity in isolated rat DRG neurons via 5-HTNeuropharmacology · 2021Article
- Current Limitations and Candidate Potential of 5-HT7 Receptor Antagonism in Psychiatric Pharmacotherapy.Frontiers in psychiatry · 2021Review
- Differential mechanisms are required for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections.Experimental neurology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Spinal serotonin type 7 (5-HT7) receptors elicit complex effects on motor activity. Whereas 5-HT7 receptor activation gives rise to long-lasting phrenic motor facilitation (pMF), it also constrains 5-HT2 receptor-induced pMF via "cross-talk inhibition." We hypothesized that divergent cAMP-dependent signaling pathways give rise to these distinct 5-HT7 receptor actions. Specifically, we hypothesized that protein kinase A (PKA) mediates cross-talk inhibition of 5-HT2 receptor-induced pMF whereas 5-HT7 receptor-induced pMF results from exchange protein activated by cAMP (EPAC) signaling. Anesthetized, paralyzed, and ventilated rats receiving intrathecal (C4) 5-HT7 receptor agonist (AS-19) injections expressed pMF for >90 min, an effect abolished by pretreatment with a selective EPAC inhibitor (ESI-05) but not a selective PKA inhibitor (KT-5720). Furthermore, intrathecal injections of a selective EPAC activator (8-pCPT-2'-Me-cAMP) were sufficient to elicit pMF. Finally, spinal mammalian target of rapamycin complex-1 (mTORC1) inhibition via intrathecal rapamycin abolished 5-HT7 receptor- and EPAC-induced pMF, demonstrating that spinal 5-HT7 receptors elicit pMF by an EPAC-mTORC1 signaling pathway. Thus 5-HT7 receptors elicit and constrain spinal phrenic motor plasticity via distinct signaling mechanisms that diverge at cAMP (EPAC vs. PKA). Selective manipulation of these molecules may enable refined regulation of serotonin-dependent spinal motor plasticity for therapeutic advantage.
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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.