As vanilloid receptor agonist

Olvanil [inn, usan] (/V-vanillyloleamide) is a capsaicin analogue regarded as a vanilloid receptor AGONIST. It can be... 

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. 

Homologs of VR1 with a high threshold (> 52°C) for activation by noxious heat, or sensitivity to membrane stretch, provisionally termed vanilloid receptor-like protein (VRL-1) (Caterina et al., 1999) and stretch-inactivated channel (SIC) (Suzuki et al., 1999), respectively, have been identified. Neither channel is activated by vanilloid agonists (Caterina et al., 1999 Suzuki et al., 1999). A mouse ortholog of VRL-1 acts as a growth factor regulated channel (GRC) permeable to Ca2+ ions (Kanzaki et al., 1999). A splice variant of VR1 (VR.5 sv) that lacks the majority of the intracellular N-terminal domain is refractory to activation by vanilloid agonists, protons or noxious... 

Daphnanes (C5 (C7 C6) include a variety of cytotoxic, irritant, inflammatory and toxic compounds from the Thymelaeaceae and the Euphorbiaceae. Of particular note are the highly inflammatory PKC activators resiniferatoxin and tinyatoxin from Euphorbia species (Euphorbiaceae) and thymeleatoxin from Thymeka hirsuta (Thymelaeaceae). While the nonester resiniferonol is inactive, the ester (X—CO—O—Y) resiniferatoxin is both an anti-nociceptive vanilloid receptor (capsaicin receptor) agonist and a PKC activator, as is the ester tinyatoxin. 

In addition to actions at cannabinoid receptors, AEA, 2AG, virodhamine, noladin ether, and NADA also act at the vanilloid receptor (transient receptor potential vanilloid type 1 TRPV1 previously know as VRl), a ligand-gated ion channel that is a member of the transient receptor potential (TRP) ion channel family (recently reviewed by Di Marzo et al. 2002). In addition, zl -THG and cannabinol at high (20 pM) concentrations have recently been identified as agonists at another TRP, the ANKTMl channel (Jordt et al. 2004). These findings raise the possibility that the TRP channels maybe ionotropic cannabinoid receptors. 

As mentioned earlier, 2-AG possesses several notable features as a signaling molecule (1) 2-AG exhibits potent cannabimimetic activities in vitro and in vivo (2) importantly, unhke anandamide, 2-AG acts as a full agonist at both the CBj receptor and the CBj receptor (3) 2-AG is rapidly and selectively produced in a variety of cells upon stimulation and is easily released into the extracellular milieu and (4) different from anandamide, 2-AG does not bind to receptors other than the cannabinoid receptors, such as the vanilloid receptor. Based on these observations, we have previously proposed that 2-AG is the true natural ligand of the cannabinoid receptors (Sugiura, Kodaka, Kondo, Nakane, etal., 1997 Sugiura, Kodaka, etal., 1999 Sugiura, Kondo, etal., 2000 for review, see Sugiura and Waku 2000). 

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