The TRPV1 vanilloid receptor: A target for therapeutic intervention

Capsaicin (1), the active component of hot chili peppers, and related irritant compounds exert their pharmacological effect via activation of an excitatory ion channel expressed on nociceptors [1]. The cellular target for 1 was cloned and characterized from a cDNA from rat sensory neurons in 1997 and named the VR1 receptor [2]. Additional members of the family were subsequently cloned in several laboratories leading to multiple names for the same receptor. This prompted the adoption of the transient receptor potential (TRP) nomenclature whereby the VR1 receptor is now known as the TRPV1 receptor [3]. This family of receptors consist of a large class of ion channels characterized by their permeability to monovalent cations and calcium ions, exhibiting a common structure made up of subunits with six membrane spanning domains [4,5]. The cloning of the rat receptor was quickly followed by the cloning of the human isoform [6] together with the characterization of TRPV1 "knockout" mice by two groups [7,8]. Knockout studies demonstrated that the receptor plays a key role as an integrator of noxious and chemical stimuli that produce pain. The receptor may be activated by heat, low pH, additional vanilloids, including the ultrapotent daphnane diterpenoid resiniferatoxin (RTX) (2), and a range of endogenous mediators encompassing products of the lipoxygenase pathway, bradykinin, and the endocannabinoid anandamide [1,9,10]. Thus numerous activators, often associated with tissue injury or inflammation, appear to operate by reducing the heat threshold of the receptor. © 2005 Elsevier Inc. All rights reserved.