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TRPM8: From Cold to Cancer, Peppermint to Pain

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Temperature perception is vital for cellular and metabolic homeostasis, avoidance, and survival. In the primary afferent nerve terminal, select members of the transient receptor potential (TRP) family of ion channels reside and convert thermal stimuli into neuronal activity. The cold and menthol receptor, TRPM8, is the predominant thermoceptor for cellular and behavioral responses to cold temperatures. Remarkably, this single molecular sensor of cold, that responds at a discrete thermal threshold in vitro (∼28°C), enables sensory afferents to respond to distinct, yet varied thermal thresholds (∼28 to <5°C). Thus, unlike other thermally-gated TRP channels which are activated at either innocuous or noxious temperatures, TRPM8 provides perception of both pleasantly cool and painfully cold. In addition to this diversity in sensory signaling, TRPM8 has an emerging role in a variety of biological systems, including thermoregulation, cancer, bladder function, and asthma. Here we summarize some key points related to TRPM8 and its potential as a drug target to treat a wide variety of physiological conditions. Nonetheless, it remains to be seen how this single “cool” molecule can serve in such a multitude of biological processes.

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Keywords: Arg842; Asn799; Asn934; Asp802; CMR1; Cold; Cold-induced asthma; Cys929; Gly805; Leu1009; Lys856; NGF receptor; PIP2; TRP channels; TRPM8; Tyr1005; Tyr745; Xenopus laevis; bladder urothelium; breast adenocarcinoma; cDNA; capsazepine; cold allodynia; colorectal cancer; iPLA2; icilin; melanoma; menthol; pain; petrosal ganglia; prostate cancer; siRNA; thermoregulation; thio-BCTC

Document Type: Research Article

Publication date: 2011-01-01

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  • Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.
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