Serotonin type-1D receptor stimulation of A-type K+ channel decreases membrane excitability through the protein kinase A- and B-Raf-dependent p38 MAPK pathways in mouse trigeminal ganglion neurons

Zhao, Xianyang; Zhang, Yuan; Qin, Wenjuan; Cao, Junping; Zhang, Yi; Ni, Jielei; Sun, Yan-Gang; Jiang, Xinghong; Tao, Jin

doi:10.1016/j.cellsig.2016.05.004

Cited by 20 publications

(24 citation statements)

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“…Different 5‐HT 1 receptor subtypes, including 5‐HT 1F , have been localised on trigeminal ganglion neurons, so that the trigeminal ganglion appears to be a target for triptans . Triptans binding to Gi‐protein–coupled 5‐HT 1 receptor subtypes may act on trigeminal ganglion neurons via different mechanisms . Sumatriptan inhibits CGRP release from the trigeminal ganglion, which can be reversed by a 5‐HT 1B/D antagonist .…”

Section: Discussionmentioning

confidence: 99%

“…Sumatriptan inhibits voltage‐gated calcium currents in rat trigeminal ganglion neurons and prevents sensitisation of neurons innervating the dura mater against inflammatory mediators, which can be blocked by a 5‐HT 1D antagonist . In addition, activation of the 5‐HT 1D receptor subtype decreases the membrane excitability of mouse trigeminal ganglion neurons Triptans probably inhibit nociceptive transmission within the trigeminal nuclear brainstem complex (TBNC).…”

Section: Discussionmentioning

confidence: 99%

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Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect

Tfelt‐Hansen

Meßlinger

2019

Brit J Clinical Pharma

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In randomised controlled trials (RCTs) of oral drug treatment of migraine attacks, efficacy is evaluated after 2 hours. The effect of oral naratriptan 2.5 mg with a maximum blood concentration (Tmax) at 2 hours increases from 2 to 4 hours in RCTs. To check whether such a delayed effect is also present for other oral antimigraine drugs, we hand‐searched the literature for publications on RCTs reporting efficacy. Two triptans, 3 nonsteroidal anti‐inflammatory drugs (NSAIDs), a triptan combined with an NSAID and a calcitonin gene–related peptide receptor antagonist were evaluated for their therapeutic gain with determination of time to maximum effect (Emax). Emax was compared with known Tmax from pharmacokinetic studies to estimate the delay to pain‐free. The delay in therapeutic gain varied from 1–2 hours for zolmitriptan 5 mg to 7 hours for naproxen 500 mg. An increase in effect from 2 to 4 hours was observed after eletriptan 40 mg, frovatriptan 2.5 mg and lasmiditan 200 mg, and after rizatriptan 10 mg (Tmax = 1 h) from 1 to 2 hours. This strongly indicates a general delay of effect in oral antimigraine drugs. A review of 5 possible effects of triptans on the trigemino‐vascular system did not yield a simple explanation for the delay. In addition, Emax for triptans probably depends partly on the rise in plasma levels and not only on its maximum. The most likely explanation for the delay in effect is that a complex antimigraine system with more than 1 site of action is involved.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect

Tfelt‐Hansen

Meßlinger

2019

Brit J Clinical Pharma

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“…All experimental and surgical procedures conformed to NIH guidelines and were approved by the Institutional Animal Care and Use Committee of Soochow University. Neurons were enzymatically dissociated from trigeminal ganglia (TG) of ICR mice (6‐8 weeks, regardless of sex) as described in our previous studies . In brief, TGs were bilaterally dissected out from anesthetized mice and the connective tissue was removed.…”

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry was conducted as described previously . Briefly, mice were anesthetized with isoflurane and transcardially perfused.…”

Section: Methodsmentioning

confidence: 99%

Melatonin‐mediated inhibition of Cav3.2 T‐type Ca²⁺ channels induces sensory neuronal hypoexcitability through the novel protein kinase C‐eta isoform

Zhang

Wang

et al. 2018

Journal of Pineal Research

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Recent studies implicate melatonin in the antinociceptive activity of sensory neurons. However, the underlying mechanisms are still largely unknown. Here, we identify a critical role of melatonin in functionally regulating Cav3.2 T-type Ca channels (T-type channel) in trigeminal ganglion (TG) neurons. Melatonin inhibited T-type channels in small TG neurons via the melatonin receptor 2 (MT receptor) and a pertussis toxin-sensitive G-protein pathway. Immunoprecipitation analyses revealed that the intracellular subunit of the MT receptor coprecipitated with Gα . Both shRNA-mediated knockdown of Gα and intracellular application of QEHA peptide abolished the inhibitory effects of melatonin. Protein kinase C (PKC) antagonists abolished the melatonin-induced T-type channel response, whereas inhibition of conventional PKC isoforms elicited no effect. Furthermore, application of melatonin increased membrane abundance of PKC-eta (PKC ) while antagonism of PKC or shRNA targeting PKC prevented the melatonin-mediated effects. In a heterologous expression system, activation of MT receptor strongly inhibited Cav3.2 T-type channel currents but had no effect on Cav3.1 and Cav3.3 current amplitudes. The selective Cav3.2 response was PKC dependent and was accompanied by a negative shift in the steady-state inactivation curve. Furthermore, melatonin decreased the action potential firing rate of small TG neurons and attenuated the mechanical hypersensitivity in a mouse model of complete Freund's adjuvant-induced inflammatory pain. These actions were inhibited by T-type channel blockade. Together, our results demonstrated that melatonin inhibits Cav3.2 T-type channel activity through the MT receptor coupled to novel G -mediated PKC signaling, subsequently decreasing the membrane excitability of TG neurons and pain hypersensitivity in mice.

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“…Other studies indicate that a decrease in I A mediates increased excitability produced by angiotensin (Moreira et al 2009) or diabetic neuropathy (Cao et al 2010). Conversely, increased I A by activation of serotonin 1D receptors decreases excitability (Zhao et al 2016). Given its well established role in controlling graded AP frequency, it is, therefore, surprising that no difference was found in the level of I A when comparing phasic or tonic neurons (Tang et al 2016).…”

Section: Membrane Properties Associated With Tonic and Phasic Firing mentioning

confidence: 99%

Morphological and functional diversity of first-order somatosensory neurons

2017

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First-order somatosensory neurons transduce and convey information about the external or internal environment of the body to the central nervous system. They are pseudo unipolar neurons with cell bodies residing in one of several ganglia located near the central nervous system, with the short branch of the axon connecting to the spinal cord or the brain stem and the long branch extending towards the peripheral organ they innervate. Besides their sensory transducer and conductive role, somatosensory neurons also have trophic functions in the tissue they innervate and participate in local reflexes in the periphery. The cell bodies of these neurons are remarkably diverse in terms of size, molecular constitution, and electrophysiological properties. These parameters have provided criteria for classification that have proved useful to establish and study their functions. In this review, we discuss ways to measure and classify populations of neurons based on their size and action potential firing pattern. We also discuss attempts to relate the different populations to specific sensory modalities.

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Serotonin type-1D receptor stimulation of A-type K+ channel decreases membrane excitability through the protein kinase A- and B-Raf-dependent p38 MAPK pathways in mouse trigeminal ganglion neurons

Cited by 20 publications

References 58 publications

Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect

Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect

Melatonin‐mediated inhibition of Cav3.2 T‐type Ca²⁺ channels induces sensory neuronal hypoexcitability through the novel protein kinase C‐eta isoform

Morphological and functional diversity of first-order somatosensory neurons

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Serotonin type-1D receptor stimulation of A-type K+ channel decreases membrane excitability through the protein kinase A- and B-Raf-dependent p38 MAPK pathways in mouse trigeminal ganglion neurons

Cited by 20 publications

References 58 publications

Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect

Why is the therapeutic effect of acute antimigraine drugs delayed? A review of controlled trials and hypotheses about the delay of effect

Melatonin‐mediated inhibition of Cav3.2 T‐type Ca2+ channels induces sensory neuronal hypoexcitability through the novel protein kinase C‐eta isoform

Morphological and functional diversity of first-order somatosensory neurons

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Melatonin‐mediated inhibition of Cav3.2 T‐type Ca²⁺ channels induces sensory neuronal hypoexcitability through the novel protein kinase C‐eta isoform