Molecular Sensors for Noxious Temperature

抄録

The transient receptor potential (TRP) channel TRPM3 is a calcium-permeable cation channel activated by heat and by the neurosteroid pregnenolone sulfate (PregS). TRPM3 is highly expressed in sensory neurons, where it plays a key role in heat sensing and inflammatory hyperalgesia. In comparison to other TRP channels involved in nociception, very little is known about the regulation of this channel and its pharmacology is poorly developed. We developed novel potent TRPM3 agonists and antagonists and a variety of combined knockout models to elucidate the in vivo roles of TRPM3 in acute and chronic pain, and establish its relative contribution to acute noxious heat sensing. Our results shed new light on the relative roles of TRPV1, TRPM3 and TRPA1 in various forms of nociception, and may form the basis for the development of novel TRPM3-targeting analgesic drugs.