A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation

Brackley, Allison Doyle; Gomez, Ruben; Guerrero, Kristi A.; Akopian, Armen N.; Glucksman, Marc J.; Du, Junying; Carlton, Susan M.; Jeske, Nathaniel Aaron

doi:10.1038/s41598-017-01999-4

Cited by 28 publications

(49 citation statements)

References 81 publications

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“…1,27 Since these kinases are known to be involved in sensitization of TRP channels, 28,29 we investigated the role of PKA and PKC in | 291 1,27 Since these kinases are known to be involved in sensitization of TRP channels, 28,29 we investigated the role of PKA and PKC in | 291…”

Section: Sensory Neuron Type-dependent Sensitization Of Trpa1 Respomentioning

confidence: 99%

“…Then, the plasmids containing mutated TRPV1 (WT TRPV1 size is 90kDa 18,35,36 ) were co-expressed with WT TRPA1 (WT TRPA1 size is 120 kDa 18,28,35,36 ) in CHO cells. Then, the plasmids containing mutated TRPV1 (WT TRPV1 size is 90kDa 18,35,36 ) were co-expressed with WT TRPA1 (WT TRPA1 size is 120 kDa 18,28,35,36 ) in CHO cells.…”

Section: Identification Of Interaction Domains For the Trpa1-trpv1 mentioning

confidence: 99%

“…All sensory neuron subgroups express substantial levels of protein kinase C epsilon (PKCε), and regulatory and catalytic subunits of cAMP-dependent kinase (PKA). 1,27 Since these kinases are known to be involved in sensitization of TRP channels, 28,29 we investigated the role of PKA and PKC in | 291…”

Section: Sensory Neuron Type-dependent Sensitization Of Trpa1 Respomentioning

confidence: 99%

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Sensitization of small‐diameter sensory neurons is controlled by TRPV1 and TRPA1 association

et al. 2019

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Unique features of sensory neuron subtypes are manifest by their distinct physiological and pathophysiological functions. Using patch-clamp electrophysiology, Ca 2+ imaging, calcitonin gene-related peptide release assay from tissues, protein biochemistry approaches, and behavioral physiology on pain models, this study demonstrates the diversity of sensory neuron pathophysiology is due in part to subtype-dependent sensitization of TRPV1 and TRPA1. Differential sensitization is influenced by distinct expression of inflammatory mediators, such as prostaglandin E 2 (PGE 2 ), bradykinin (BK), and nerve growth factor (NGF) as well as multiple kinases, including protein kinase A (PKA) and C (PKC). However, the co-expression and interaction of TRPA1 with TRPV1 proved to be the most critical for differential sensitization of sensory neurons. We identified N-and C-terminal domains on TRPV1 responsible for TRPA1-TRPV1 (A1-V1) complex formation. Ablation of A1-V1 complex with dominant-negative peptides against these domains substantially reduced the sensitization of TRPA1, as well as BK-and CFA-induced hypersensitivity. These data indicate that often occurring TRP channel complexes regulate diversity in neuronal sensitization and may provide a therapeutic target for many neuroinflammatory pain conditions. K E Y W O R D Spain, sensitization, sensory neurons, TRPA1, TRPV1 288 | PATIL eT AL.

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Section: Sensory Neuron Type-dependent Sensitization Of Trpa1 Respomentioning

confidence: 99%

Section: Identification Of Interaction Domains For the Trpa1-trpv1 mentioning

confidence: 99%

Section: Sensory Neuron Type-dependent Sensitization Of Trpa1 Respomentioning

confidence: 99%

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Sensitization of small‐diameter sensory neurons is controlled by TRPV1 and TRPA1 association

et al. 2019

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“…The present study showed that a carboplatin-induced increase in sensitivity to TRPA1 was significantly decreased by not only a PKA inhibitor but also an AKAP inhibitor ( Figures 5 and 6). AKAP, a scaffolding protein, is required for PKA activation, and it enhances the sensitization of several receptors and ion channels via PKA [38][39][40][41]. Brackley et al [41] have reported that AKAP facilitates phosphorylation of TRPA1, and increases the sensitivity of DRG neurons to TRPA1.…”

Section: Discussionmentioning

confidence: 99%

Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways

Miyano¹,

Shiraishi²,

Minami

et al. 2019

Preprint

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Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is involved not only in pain transmission but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

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“…TRPA1 is demonstrated to be cold sensitive [61] and plays roles in both cold transduction and mechanotransduction in cutaneous sensory neurons. AKAP 79/150 facilitates phosphorylation and sensitization of TRPA1 in peripheral sensory neurons, resulting in persistent mechanical hypersensitivity [62]. Another study also indicated that TRPA1 activation could co-sensitize TRPV1 channels [60].…”

Section: Other Trp Receptorsmentioning

confidence: 98%

Peripheral Sensitization

Wei¹,

Tao²,

Yang³

et al. 2020

Peripheral Nerve Disorders and Treatment

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Peripheral sensitization indicates increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation, which usually occurs after peripheral tissue injury and inflammation. As an integral part of pain, peripheral sensitization and its mechanisms have received much attention, and numerous types of neurotransmitters and chemicals related to peripheral sensitization were investigated. We developed an animal model of peripheral sensitization, and it provides evidence that some neurotransmitters, such as glutamate and substance P, release from adjacent peripheral nerves contributing to the peripheral sensitization of pathological pain. In this chapter, we reviewed the advances in peripheral sensitization, and it will provide a basis for new targets to attenuate pain of peripheral origin.Several animal models of various pain states have been established to investigate the mechanisms of peripheral sensitization, for example, inflammation pain models, neuropathic pain evoked by disease or damage to peripheral nerves, and post-operative pain models. Animal models of inflammatory pain have used a number of different irritants that are injected into skin, paw, muscle, joint, and visceral organ. Carrageenan, complete Freund's adjuvant (CFA), and capsaicin are commonly used inflammatory irritants to induce hyperalgesia. Common nerve injury models include: (1) ligating or transecting the spinal nerves, such as spinal nerve ligation model (SNL); (2) ligating or lesioning the sciatic nerve, such as chronic constriction injury (CCI); and (3) ligating distal branches (peroneal and tibial) of the sciatic nerve (spared nerve injury) [16].To better understand the mechanisms of transmission between peripheral sensory nerve endings, we have successfully established an electrophysiological animal model in which antidromic electrical stimulation of a sensory nerve excites the adjacent primary afferents from the different spinal segments [17]. In this model, two adjacent cutaneous branches of spinal dorsal rami in the thoracic segments, T9 and T10, were dissociated and transected proximally from the spinal cord in anesthetized rats. Then antidromic electrical stimulation with 0.5 ms pulse duration, 20 Hz frequency, and 1 mA intensity was applied to T9 spinal nerve branch, and the nerve activities of T10 nerve branch were recorded [18]. All recorded afferent neurons from the T10 cutaneous branch were classified as Aβ, Aδ, and C fibers according to the conduction velocity and the receptive properties [19]. The discharges of the isolated Aβ, Aδ, and C fibers of the T10 cutaneous branch were significantly enhanced by antidromic electrical stimulation of the adjacent T9 spinal nerve branch [18]. It is in line with our previous studies that antidromic stimulation of T9 spinal nerve branch can activate and sensitize Aβ, Aδ, and C fibers obtained from the adjacent T10 dorsal cutaneous branch [20][21][22][23]. The activation and sensitization of these fibers not only occur between the peripheral sensory nerve...

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A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation

Cited by 28 publications

References 81 publications

Sensitization of small‐diameter sensory neurons is controlled by TRPV1 and TRPA1 association

Sensitization of small‐diameter sensory neurons is controlled by TRPV1 and TRPA1 association

Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways

Peripheral Sensitization

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