Potentiation of acid-sensing ion channel activity by the activation of 5-HT2 receptors in rat dorsal root ganglion neurons

Qiu, Fang; Qiu, Chun‐Yu; Liu, Yu-Qiang; Wu, Dan; Li, Jia‐Da; Hu, Wang‐Ping

doi:10.1016/j.neuropharm.2012.04.034

Cited by 38 publications

(35 citation statements)

References 44 publications

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“…The exact mechanism of sensitization is not clear from these studies. Activation of the 5‐HT2 receptor potentiates ASIC currents and shifts the pH‐dependence of activation curve upward and to slightly more neutral pH while 5‐hydroxytryptamine receptors (5‐HT) was shown recently to directly potentiate ASIC3 . Thus, it is possible that sensitization of ASICs by 5‐HT released from mast cells could lead to the enhanced sensitivity to pH change in dural afferents.…”

Section: Discussionmentioning

confidence: 99%

pH‐Evoked Dural Afferent Signaling Is Mediated by ASIC3 and Is Sensitized by Mast Cell Mediators

et al. 2013

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Background Prior studies have shown that decreased meningeal pH activates dural afferents via opening of acid-sensing ion channels (ASICs) suggesting one pathophysiological mechanism for the generation of headaches. The studies described here further examined the ASIC subtype mediating pH-induced dural-afferent activation and examined whether sensitization influences pH responses. Objective Given the potential importance of meningeal mast cells to headache, the goal of this study was to evaluate dural afferent responses to pH following sensitization with mast cell mediators. Methods Cutaneous allodynia was measured in rats following stimulation of the dura with decreased pH alone or in combination with mast cell mediators. Trigeminal ganglion neurons retrogradely-labeled from the dura were stained with an ASIC3 antibody using immunohistochemistry. Currents and action potentials evoked by changes in pH alone or in combination with mast cell mediators were measured in retrogradely-labeled dural afferents using patch-clamp electrophysiology. Results pH-sensitive dural afferents generated currents in response to the ASIC3 activator 2-guanidine-4-methylquinazoline (GMQ), approximately 80% of these neurons express ASIC3 protein, and pH-evoked behavioral responses were inhibited by the ASIC3 blocker APETx2. Following exposure to mast cell mediators, dural afferents exhibited increased pH-evoked excitability and cutaneous allodynia was observed at higher pH than with pH stimuli alone. Conclusion These data indicate that the predominant ASIC subtype responding to decreased meningeal pH is ASIC3. Additionally, they demonstrate that in the presence of inflammation, dural afferents respond to even smaller decreases in pH providing further support for the ability of small pH changes within the meninges to initiate afferent input leading to headache.

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Section: Discussionmentioning

confidence: 99%

pH‐Evoked Dural Afferent Signaling Is Mediated by ASIC3 and Is Sensitized by Mast Cell Mediators

et al. 2013

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“…A critical role for histamine in pain is not restricted to allergic inflammatory conditions but is also an important mediator of neuropathic pain induced by sciatic nerve ligation [48] and inflammatory pain induced by AITC, capsaicin, and formalin [49–51]. 5-HT binding to 5-HT2 receptor and PKC activation increases the expression of neuronal acid-sensing ion channels (ASICs), which sense extracellular protons and mediate increased pain signaling [52]. …”

Section: Modulation Of Pain Sensitivity By Immune Cellsmentioning

confidence: 99%

Nociceptor Sensory Neuron–Immune Interactions in Pain and Inflammation

Pinho‐Ribeiro

Verri

Chiu

2017

Trends in Immunology

704

626

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Nociceptor sensory neurons protect organisms from dangers by eliciting pain and driving avoidance. Pain also accompanies many types of inflammation and injury. It is increasingly clear that active crosstalk occurs between nociceptor neurons and the immune system to regulate pain, host defense, and inflammatory diseases. Immune cells at peripheral nerve terminals and within the spinal cord release mediators that modulate mechanical and thermal sensitivity. In turn, nociceptor neurons release neuropeptides and neurotransmitters from nerve terminals that regulate vascular, innate, and adaptive immune cell responses. Therefore, the dialogue between nociceptor neurons and the immune system is a fundamental aspect of inflammation, both acute and chronic. A better understanding of these interactions could produce approaches to treat chronic pain and inflammatory diseases.

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“…Another study supported the involvement of 5-HT 2 receptors in 5-HT-induced hyperalgesia, which was inhibited by 5-HT 2 antagonists in DRG neurons (96). Moreover, activation of 5-HT 2 receptors potentiated the activity of ASICs in rat DRG neurons via protein kinase C (PKC)-dependent signaling pathways (93). ASICs have a PDZ-binding domain at their C-termini, and interact with PDZ-containing proteins.…”

Section: Modulation Of Asics By Gpcrsmentioning

confidence: 79%

“…5-HT establishes pain sensation and hyperalgesia through sensitizing nociceptive afferents (93). Proinflammatory mediators such as 5-HT, bradykinin, NGF, and interleukin-1 are known to enhance the activity and the expression levels of ASICs.…”

Section: Modulation Of Asics By Gpcrsmentioning

confidence: 99%

Acid-sensing ion channels (ASICs): therapeutic targets for neurological diseases and their regulation

Kweon¹,

Suh²

2013

BMB Reports

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Extracellular acidification occurs not only in pathological conditions such as inflammation and brain ischemia, but also in normal physiological conditions such as synaptic transmission. Acid-sensing ion channels (ASICs) can detect a broad range of physiological pH changes during pathological and synaptic cellular activities. ASICs are voltage-independent, proton-gated cation channels widely expressed throughout the central and peripheral nervous system. Activation of ASICs is involved in pain perception, synaptic plasticity, learning and memory, fear, ischemic neuronal injury, seizure termination, neuronal degeneration, and mechanosensation. Therefore, ASICs emerge as potential therapeutic targets for manipulating pain and neurological diseases. The activity of these channels can be regulated by many factors such as lactate, Zn2+, and Phe-Met-Arg-Phe amide (FMRFamide)-like neuropeptides by interacting with the channel’s large extracellular loop. ASICs are also modulated by G protein-coupled receptors such as CB1 cannabinoid receptors and 5-HT2. This review focuses on the physiological roles of ASICs and the molecular mechanisms by which these channels are regulated. [BMB Reports 2013; 46(6): 295-304]

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Potentiation of acid-sensing ion channel activity by the activation of 5-HT2 receptors in rat dorsal root ganglion neurons

Cited by 38 publications

References 44 publications

pH‐Evoked Dural Afferent Signaling Is Mediated by ASIC3 and Is Sensitized by Mast Cell Mediators

pH‐Evoked Dural Afferent Signaling Is Mediated by ASIC3 and Is Sensitized by Mast Cell Mediators

Nociceptor Sensory Neuron–Immune Interactions in Pain and Inflammation

Acid-sensing ion channels (ASICs): therapeutic targets for neurological diseases and their regulation

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