Vanilloid receptor subtype

Capsaicin (52 Qutenza ) Capsaicin (52) Vanilloid NP Plant Pain Binds to the ion channel receptor vanilloid receptor subtype 1 (VR 1) 460 66... 

Hot peppers and painful heat both activate sensory nerve fibers through an ion channel, known as vanilloid receptor subtype 1 (VR1). When activated, the channel opens, allowing an influx of calcium and sodium ions. The influx depolarizes neuronal pain fibers, initiating a nerve impulse through the dorsal root ganglion (DRG) to the brain. Noxious heat also activates VR1, explaining why our mouths feel hot when we eat chilli peppers. 

Epidermis is an interface between body and environment. The basic mechanism of the smart system of the epidermis has not been clarified yet, but epidermal ion dynamics in the epidermis plays an important role as a signaling system.47,49 As described earlier, a variety of receptors of neurotransmitters are found in the keratinocytes. Recently, the existence and function of vanilloid receptor subtype 1 (VR1, TRPV1) in epidermal keratinocytes has been demonstrated (Figure 10.2).50,51... 

It irritates skin and mucous membranes. In terms of chemoreception, it irritates the trigeminal nerve. Capsaicin binds to the vanilloid receptor subtype 1 (VRl). Birds lack this receptor. Since they cannot sense capsaicin, they eat and distribute seeds of red hot peppers. Medically capsaicin is used as painkiller (analgesic). 

Mezey E, Toth ZE, Cortright DN, Arzubi MK, Krause JE, Elde R, Guo A, Blumberg PM, Szallasi A (2000) Distribution of mRNA for vanilloid receptor subtype 1 (VRl), and VRl-like immunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci USA 97 3655-3660... 

Ventresca PG, Nichol CM, Barnes PJ, Chung KF (1990) Inhaled furosemide inhibits cough induced by low chloride content solutions but not by capsaicin. Am Rev Respir Dis 142 143-146 Wang L, Bradley RM (1995) In vitro study of afferent synaptic transmission in the rostral gustatory zone of the rat nucleus of the solitary tract. Brain Res 702 188-198 Watanabe N, Horie S, Michael GJ, Spina D, Page CP, Priestley JV (2005) Immunohistochemical localization of vanilloid receptor subtype 1 (TRPV1) in the guinea pig respiratory system. Pulm Pharmacol Ther 18 187-197... 

Innovative uses for novel, receptor subtype-selective vanilloids (see below), e.g. weight control. 

VANILLOID RECEPTOR ANTAGONISTS act at sites activated by sensory irritants, e.g. capsaicin see VANILLOID receptor agonists. Capsazepine, a synthetic compound developed out of vallinoids such as capsaicin, is a high-afflnity competitive vanilloid receptors antagonist. It is used as a pharmacological tool. There is some variation in affinity between different sites and species, suggesting receptor subtypes and species variants. Ruthenium Red also acts as an inhibitor at these sites in a non-competitive manner. 

It clearly appears that if the endocannabinoid system really plays a role in the physiopathology of schizophrenia, the activation of CBj receptors does not seem to be a crucial point. Interestingly, CBi is not the sole CB receptor subtype expressed in the brain. Some studies using CB, KO mice supported the existence of G-protein-coupled non-CBj and non-CBj cannabinoid receptors, sensitive to endocannabinoids, synthetic agonists, and rimonabant (Di Marzo et al., 2000 Breivogel et al., 2001 Pride et al., 2003). In addition, anandamide has been found to activate both CB, and vanilloid VR, receptors (for review see Di Marzo et al., 2002). However, the localizations and functions of such types of receptors are unclear, and their putative role in schizophrenia remains to be demonstrated. Although cannabis use appears to be neither a sufficient nor a necessary cause for psychosis, the current status of research on cannabis-associated psychosis (Leweke et al., 2004) is inconclusive, and further research is needed to understand the mechanisms by which cannabis is associated with psychosis. 

TRPV channels are further classified into six subfamilies TRPVl, TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6. The subtypes TRPV 1, 2, 3, and 4 are called thermo TRPs [4] since all of them are activated by different degrees of temperature. In 1997 the TRPVl (capsaicin, vanilloid) receptor was cloned from rodent posterior dorsal root ganglia [2] and since then has been studied extensively. Activation of TRPVl receptors is associated with pain formation... 

The pharmacological mechanism of action of capsaicin has been extensively reviewed [78]. In 1997, Julius and coworkers isolated and cloned the molecular target of capsaicin, a cellular transmembrane protein and a nonselective cation-permeable pore region (channel) named transient receptor potential vanilloid subtype 1 (TRPVl, also known as vanilloid receptor for its interaction with capsaicinoids) [79]. The TRPVl receptor is found in primary afferent polymodal C-fibers and A8-fibers. C-Fibers are responsible for the burning sensations, while A8-fibers are responsible for the temperature (cold and hot), pressure (mechano), and pain sensations. Both fibers are located in... 

Once released, extracellular endo cannabinoids act mostly, and with varying selectivity, on cannabinoid receptors, possibly including subtypes other than CBi and (TL. However, endocannabinoids such as AEA and/or NADA may also act, prior to their release, on intracellular sites on ion channels, such as those on vanilloid TRPVl (transient receptor potential vanilloid type 1) receptors and T-type ((a channels (see below). In this case, release represents a possible way to inactivate, rather than facilitate, the action of endocannabinoids. 

The mammalian vanilloid subtype 1 capsaicin receptor (VRlr) has been cloned and shown to be activated by plant-derived agonists such as capsaicin (the pungent ingredient in hot chili pepper) and resiniferatoxin (Caterina etal., 1997). Anandamide has been shown to activate the VRlr, resulting in physiological responses that are capsazepine-sensitive and CBR-insensitive (Zygmunt etal., 1999 and Szolcsanyi, 2000). It has also been demonstrated that anandamide acts as full... 

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