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TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues. TRPM8 also has several conserved cholesterol-binding motifs where cholesterol can bind in different modes and energies. We suggest that mutations and/or physiological conditions can potentially alter these TRPM8-cholesterol complexes and can lead to physiological disorders or even apparently irreversible diseases such as cancer and neurodegeneration.
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http://dx.doi.org/10.1007/s00232-024-00319-y | DOI Listing |
ACS Omega
September 2025
Neuroscience and Ageing Biology Division, CSIR- Central Drug Research Institute (CDRI), Lucknow 226031, India.
The TRPA1 channel has recently emerged as a critical target for pain relief since its antagonists target the beginning of the pain transduction pathway and, thus, are devoid of side effects such as sedation, dizziness, somnolence, or cognitive impairment. Despite this clinical significance, currently, no TRPA1 inhibitors suitable for therapeutic usage exist to target these channels. Since ancient times, natural products have been known to be a rich source of new drugs, useful therapeutic agents, as well as pharmacological tools.
View Article and Find Full Text PDFJ Biol Chem
June 2025
Department of Pharmacology and, School of Pharmacy, Qingdao University Qingdao Medical College, Qingdao, China; Institute of Innovative Drugs, Qingdao University, Qingdao, China. Electronic address:
Topical application of natural phenolic compound rosmarinic acid (ROSA) and its analogs is known to exert pharmacological effects, including anti-inflammation, antiallergy, and antioxidant properties. However, the mechanism of action of the ROSA remains largely unknown. Here, we describe a novel role of natural phenolic ROSA and its analogs in the selective inhibition of warmth-sensitive Ca-permeable cutaneous TRPV3 channel for the alleviation of skin lesions through the downregulation of NF-κB pathway.
View Article and Find Full Text PDFMolecules
August 2024
Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, 1 Ningde Road, Qingdao 266073, China.
Natural caffeic acid (CA) and its analogues have been studied for their potential applications in the treatment of various inflammatory and infectious skin diseases. However, the molecular mechanism underlying the effects of the CA remains largely unknown. Here, we report that CA and its two analogues, caffeic acid phenethyl ester (CAPE) and caffeic acid methyl caffeate (CAMC), inhibit TRPV3 currents in their concentration- and structure-dependent manners with IC values ranging from 102 to 410 μM.
View Article and Find Full Text PDFJ Membr Biol
December 2024
School of Biological Sciences, National Institute of Science Education and Research, An OCC of Homi Bhabha National Institute, Khordha, Jatni, Odisha, 752050, India.
TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues.
View Article and Find Full Text PDFZhonghua Yi Xue Za Zhi
January 2024
Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
To explore the effects between transient receptor potential melastatin 8 (TRPM8) on pain symptom and neuronal proliferation in mice with interstitial cystitis/bladder pain syndrome (IC/BPS). Female wild-type C57BL/6 mice (8-10 weeks old) were divided into control group, IC/BPS model group, and IC/BPS model+menthol group (6 mice each) by random number table method; TRPM8 knockout mice were randomly divided into TRPM8 knockout group and TRPM8 knockout model group (6 mice each). The IC/BPS model group, the IC/BPS model+menthol group, and the TRPM8 knockout model group were injected subcutaneously with residues 65-84 of murine uroplakin 3A (UPK3A65-84).
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