The Emerging Pharmacology of TRPM8 Channels: Hidden Therapeutic Potential Underneath a Cold Surface
Abstract:Transient receptor potential melastatin 8 (TRPM8) is a non-selective cation channel activated by cold temperature and cooling agents. TRPM8 is expressed in a subpopulation of cold-sensitive sensory neurons, as well as in the male urogenital system. TRPM8 is markedly upregulated in prostate cancer and in other tumors such as breast adenocarcinoma and melanoma. Moreover, recent studies suggest the potential involvement of TRPM8 channels in the pathophysiology of cold nociception and cold allodynia. This has led to a strong interest in the pursuit of novel modulators of TRPM8 channels. This review highlights our current knowledge of TRPM8 pharmacology and modulation mechanisms, detailing structural features important for TRPM8 gating by different agonists, the mechanism of antagonism by different compounds and the potential relevance of TRPM8 for treatment of various pathological conditions.
Keywords: A fibers; AMTB; Asp802; C-fibers; Calcium Imaging Microscopy; Cold; DRG neurons; HEK293 cells; Leu1009; MWCmodel; Patch-Clamp Electrophysiology; S4-S5 linker; SKF96365; Ser9; TRPM8 Channels; TRPM8 agonist; TRPM8 gene; TRPM8 modulators; TRPM8-expressing neurons; TRPV1; Thr17; Transient receptor potential melastatin; Tyr745; WS-12; Y745H mutant; bladder urothelium; breast adenocarcinoma; citronellal; cold allodynia; cold nociception; desensitization; detrusor overactivity; geraniol; hippocampal neurons; human prostate carcinoma; linalool; male urogenital tract; melanoma; menthol; menthol affinity; neuroendocrine tumor; pain; peripheral sensory neurons; prostate cancer; prostate epithelium; putative phosphorylation sites; rat myocytes; thermoreceptor; trigeminal ganglia; unmyelinated afferents; vasomotor responses; voltage clamp errors; voltage-gated potassium (Kv) channels
Document Type: Research Article
Publication date: 2011-01-01
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