Capsaicin endogenous Vanilloids

Naturally Occurring Analogs and Antagonists of Capsaicin and Endogenous Vanilloids 193... 

Huang etal. assumed that N-arachidonoyl-dopamine (NADA) may exist as an endogenous capsaicin-like cannabinoid in mammalian nervous tissues and may possibly bind to the vanilloid receptor VRl. They found that NADA is indeed a natural endocannabinoid, in nervous tissues, with high concentrations found in the striatum, hippocampus, and cerebellum. They were also found in lower concentrations in the dorsal root ganglion. NADA binds to the cannabinoid receptors with a 40-fold selectivity for the CBi (K = 250 it 130 nM) over the CB2 receptors. 

Figure 30-29 Structures of the active components of cannabis, tetrahydrocannabinol, and cannabidiol, and structures of endogenous cannabinoids and of the vanilloid lipid capsaicin.

Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F, Tognetto M, Petros TJ, Krey JF, Chu CJ, Miller JD, Davies SN, Geppetti P, Walker JM, Di Marzo V (2002) An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VRl receptors. Proc Natl Acad Sci USA 99 8400-8405... 

Capsaicin is a naturally occurring substance derived from hot chUi peppers of the genus Capsicum. Capsaicin interacts with the vanilloid receptor (VRl) on sensory afferents. VRl is a gated cation channel of the TRP family, modulated by a variety of noxious stimuli. Chronic exposure to capsaicin stimulates and desensitizes this channel. Capsaicin also causes local depletion of substance P, an endogenous neuropeptide involved in sensory perception and pain transmission. Capsaicin is available as a 0.025% cream (zostrix, others) and a 0.075% cream (zostrix hp, others) to be applied 3-4 times daily. Capsaicin is FDA-approved for the treatment of postherpetic neuralgia and painful diabetic neuropathy, although its efficacy in relieving pain is debatable. 

An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VRl receptors, Proceedings of the National Academy of Sciences of the USA 99 8400-8405. 

Hwang SW, Cho H, Kwak J, et al. (2000) Direct activation of capsaicin receptors by products of hpoxygenases endogenous capsaicin-like substances. Proc Natl Acad Sci USA 97 6155-6160 Inoue K, Koizumi S, Fuziwara S, et al. (2002) Functional vanilloid receptors in cultured normal human epidermal keratinocytes. Biochem Biophys Res Commun 291 124-129 Ishiura Y, Fujimura M, Nobata K, et al. (2007) Prostaglandin 12 enhances cough reflex sensitivity to capsaicin in the asthmatic airway. Cough 3 2... 

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