Beyond Hot and Spicy: TRPV Channels and their Pharmacological Modulation

Seebohm, Guiscard; Schreiber, Julian A.

doi:10.33594/000000358

Cited by 32 publications

(14 citation statements)

References 141 publications

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“…Besides R557, residues Y511 and S512 from S3 segment, and M547 and T550 from S4 segment, are also essential for agonistic effect of capsaicin as mutations Y511A or S512Y of rTRPV1 abolish the channel sensitivity to capsaicin. This indicates that these key residues also contribute to CPIPC -mediated activation of TRPV1 [ 39 , 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Partial and Selective TRPV1 Agonist CPIPC for Alleviation of Inflammatory Pain

Dong

Zhou²,

Liang

et al. 2022

Molecules

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Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, predominantly expressed in a subset of peripheral sensory neurons for pain signaling. Topical application of agonist capsaicin for desensitizing TRPV1 currents has been approved for relief of chronic pain. However, the potent TRPV1 capsaicin is not ingestible and even topical capsaicin causes common side effects such as skin irritation, swelling, erythema and pruritus, suggesting that a mild TRPV1 agonist might be helpful for reducing side effects while reliving pain. In this study, we reported on a partial and selective TRPV1 agonist 4-(5-chloropyridin-2-yl)-N-(1H-indazol-6-yl)piperazine-1-carboxamide named CPIPC that was modified based on targeting the residue Arg557, important for conversion between the channel antagonism and agonism. Whole-cell patch clamp recordings indicated a concentration-dependent activation of TRPV1 currents by CPIPC with an EC50 of 1.56 ± 0.13 μM. The maximum efficacy of CPIPC (30 μM) was about 60% of saturated capsaicin (10 μM). Repetitive additions of CPIPC caused TRPV1 current desensitization in both TRPV1-expressing HEK293 cells and dorsal root ganglion (DRG) sensory neurons. Oral administration of CPIPC dose-dependently alleviated inflammatory pain in mice. Further site-directed mutagenesis combined with molecular docking revealed that residue Arg557 is critical for TRPV1 activation by CPIPC. Taken together, we identified a novel partial and selective TRPV1 agonist CPIPC that exhibits antinociceptive activity in mice.

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Section: Discussionmentioning

confidence: 99%

Identification of a Partial and Selective TRPV1 Agonist CPIPC for Alleviation of Inflammatory Pain

Dong

Zhou²,

Liang

et al. 2022

Molecules

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“…The need to find new therapeutic strategies must be oriented to a complete identification of the involved receptors. TRPV receptors are involved in a plethora of physiological and pathological conditions, which makes them promising pharmacological targets [33]. Some doubts remain about the feasibility of administering specific TRPV1 agonists and antagonists in vivo due to the high probability to induce side effects as a consequence of their wide distribution in different cells and tissues [19].…”

Section: Discussionmentioning

confidence: 99%

TRPV1 Receptor Identification in Bovine and Canine Mitral Valvular Interstitial Cells

Vercelli

Gambino

Amadori

et al. 2021

Veterinary Sciences

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Myxomatous mitral valve degeneration (MMVD) is the most common acquired cardiac disease in canine species, and valvular interstitial cells (VICs) are considered the main responsible for the development of this pathology. The scientific interest is focused on isolating and characterizing these cells. The aims of the present study were to verify a novel VICs mechanical isolation method and to characterize isolated cells using immunocytochemistry and immunofluorescence, with parallel histological and immunohistochemistry assays on bovine and canine healthy and MMVD mitral valves. Antibodies against vimentin (VIM), smooth muscle actin (SMA), von Willebrand (vW) factor, Transforming Growth Factor (TGF) β1, and Transient Receptor Potential Vanilloid 1 (TRPV1) were used. The isolation method was considered reliable and able to isolate only VICs. The different assays demonstrated a different expression of SMA in healthy and MMVD mitral valves, and TRPV1 was isolated for the first time from bovine and canine VICs and the correspondent mitral valve leaflets. The novelties of the present study are the new isolation method, that may allow correlations between laboratory and clinical conditions, and the identification of TRPV1, which will lead to further investigations to understand its function and possible role in the etiology of MMVD and to the design of new therapeutic strategies.

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“…TRPV channels in the CNS play a great role not only in pain but also in neuropsychiatric disorders, such as depression, stress, and anxiety ( Singh et al, 2019 ). It was found that all kinds of tissues and organs with TRPV channels expression contribute to a plethora of physiological or pathophysiological effects ( Seebohm and Schreiber, 2021 ).…”

Section: Transient Receptor Potential Vanilloid Channelsmentioning

confidence: 99%

Relationship between acupuncture and transient receptor potential vanilloid: Current and future directions

Luo

Liu

Zhang

et al. 2022

Front. Mol. Neurosci.

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Acupuncture is a common complementary and alternative therapy around the world, but its mechanism remains still unclear. In the past decade, some studies indicated that transient receptor potential vanilloid (TRPV) channels play a great role in the response of acupuncture stimulation. In this article, we discussed the relationship between acupuncture and TRPV channels. Different from inhibitors and agonists, the regulation of acupuncture on TRPV channels is multi-targeted and biphasic control. Acupuncture stimulation shows significant modulation on TRPV1 and TRPV4 at the autonomic nervous system (ANS) including central and peripheral nervous systems. On the contrary, the abundant expression and functional participation of TRPV1 and TRPV4 were specific to acupuncture stimulation at acupoints. The enhancement or inhibition of TRPV channels at different anatomical levels will affect the therapeutic effect of acupuncture. In conclusion, TRPV channels help to understand the principle of acupuncture stimulation, and acupuncture also provides a potential approach to TRPV-related trials.

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Beyond Hot and Spicy: TRPV Channels and their Pharmacological Modulation

Cited by 32 publications

References 141 publications

Identification of a Partial and Selective TRPV1 Agonist CPIPC for Alleviation of Inflammatory Pain

Identification of a Partial and Selective TRPV1 Agonist CPIPC for Alleviation of Inflammatory Pain

TRPV1 Receptor Identification in Bovine and Canine Mitral Valvular Interstitial Cells

Relationship between acupuncture and transient receptor potential vanilloid: Current and future directions

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