Nociception, the process of detecting noxious chemical, mechanical, or thermal stimuli, occurs predominantly at the peripheral terminal neurons known as polymodal nociceptors. Nociceptors transduce noxious stimuli into membrane depolarization that triggers action potential, conducts the action potential from the sensory sites to the synapses in the CNS, and conversion of action potentials invokes a perception of pain, discomfort, and appropriate mechanical/physical protective reflexes. At the molecular level, nociception is carried out by ion channels or receptors. Plant derived vanilloid compounds (capsaicin and its ultrapotent analog, resiniferatoxin, etc.) are known to selectively depolarize nociceptors and elicit a sensations of burning pain - the sensation that is typically obtained by 'hot chili peppers". Therefore, capsaicin mimics the action of physiological/endogenous stimuli that activates the "nociceptive pathway". Recent advances in pain biology have identified receptors for vanilloids, protons (i.e., acidic solutions), and for heat.

Capsaicin receptor, termed vanilloid receptor subtype 1 (VR1), has been cloned from sensory neurons. VR1 protein is a heat-gated cation channel that exchanges ~10 Ca+ ions for every Na+ ion resulting into neuronal membrane depolarization and elevated intracellular Ca+ levels. Over-expression of VR1 caused cell death because of continuos influx of Ca+ ions. VR1 is also activated by noxious heat (elevation in temperature causing pain) and high proton concentrations (pH <6.0). Rat VR1 encodes a membrane protein of 838 aa (~95 kDa) with 6 transmembrane domains. The cytoplasmic, N-terminal hydrophilic segment (432 aa) contains a relatively proline rich region followed by three ankyrin-repeat domains. The C-terminus (154 aa) has no identifiable proteins motifs. Structurally, VR1 closely resembles putative store-operated channels (SOC) similar to Drosophila retinal proteins TRP (transient receptor protein channel) and TRPL. This family of proteins mediates the entry of extracellular calcium into cells in response to depletion of intracellular Ca+ stores. However, VR1 does not appear to be a functional SOC. VR1 expression is limited to sensory neurons.

Recently, a structural homolog of VR1, termed VRL-1 (VR1 like proteins; rat 761 aa, human 764 aa) have been cloned and characterized. There is ~49% identity between VRL-1 and VR1. In contrast to VR1, VRL-1 does not respond to capsaicin, acid or moderate heat. Instead, it is activated by high temperatures with a threshold of ~52oC. Within sensory ganglia, VRL-1 is most prominently expressed by a subset of medium to large-diameter neurons, making it a candidate receptor of transducing high-threshold heat responses. VRL-1 is also expressed in many non-neuronal tissues (lung, spleen, and intestine) that are unlikely to encounter temperatures of >50oC. It is possible that VRL-1 is also activated by stimuli other than heat.

ADI has produced highly specific rabbit antibodies to VR-1 and VRL-1 using peptide sequences specific to each protein. These antibodies should be useful in studying structure and function of vanilloid receptors.
 

m=mouse; r=rat; h=human; rb=rabbit; ~CT or ~NT=near C or N-terminus.

"Neat Antisera" are the unpurified antiserum and it is suitable for ELISA and Western.
"Affinity pure" antibodies have been over the antigen-affinity column and recommended for immunohistochemical applications.
"Control peptides" can not be used for Western as they are very short peptides. They are intended for ELISA or antibody competition studies.