TRPV1 ligands and the airway inflammatory response

In addition to the stimulation of airway C-fibres, capsaicin has also been shown to have effects on the inflammatory response as assessed in human cell-based assay systems. Thus, capsaicin has been shown to interact with TRPV1 expressed by BEAS-2B and other airway epithelial cells to cause the calcium-dependent production of cytokines and, conversely, calcium-independent cell death. The mechanisms of these cellular responses to capsaicin appear to proceed via distinct cellular pathways, but...

NADA and TRVP1

NADA (Fig. 1) has been identified in nervous tissue 10 . This novel endovanilloid is produced in highest concentrations in the striatum, hippocampus, and cerebellum. In HEK-293 cells overexpressing TRPV1 receptors, NADA increases intracellular Ca2+ levels with an EC50 of approx. 50 nM that is comparable to that obtained with capsaicin. In cultured DRG neurons, NADA increases intracellular Ca2+ levels with an EC50 of approx. 800 nM, an effect that is inhibited by capsazepine and iodoR-TX. The...

Other possible applications of intravesical TRPV1 agonists

Trpv1 The Spinal Cord

Intravesical administration of capsaicin 6 or RTX 7 can prevent pain induced by acute bladder inflammation in the rat, as shown by the suppression of c-fos gene expression in the spinal cord. An eventual analgesic effect of intravesical vanilloids in pain generated by chronic inflammatory bladder conditions would, therefore, be extremely relevant in a clinical setting. Chronic inflammatory pain is frequently disproportional to the intensity of the stimulus and is more resistant to common...

Specific contributions of TRPV1 to GI function in health and disease

Capsaicin as a neuropharmacology tool demonstration that sensory neurons are important for gut function Red pepper has been used since ancient times as both a spice and a treatment for GI disease. However, the biological actions of its pungent ingredient were not understood before capsaicin was found to be a selective stimulant of primary afferent neurons. The immediate but transient excitation is followed by a long-lasting desensitization of sensory neurons to capsaicin and other stimuli 27,...

Nociceptor hyperactivity

Desensitization of nociceptive nerve fibers may constitute an important therapeutic intervention if they are hyperactive. Following acute injury, the basis for the hyper-activity and or hypersensitivity of nociceptive nerve endings in affected tissues is well established 3 , and the protective behaviors which result from nociceptor hyperactivity are considered fundamental to tissue repair and avoidance of additional damage. Still, TRPV1-agonist-based therapies are being developed for acute...

TRPV1 antagonists

It is becoming increasingly apparent that broad in vitro antagonist activity against multiple modes of TRPV1 activation (i.e. capsaicn-site agonists, low pH and heat) may be an important predictor of in vivo efficacy in animal models of pain (see below). While some of these molecules have been tested against these various mechanisms of TRPV1 activation, many still require further pharmacological characterization. A clear understanding at the molecular level, in conjunction with pharmacokinetic...

Diversity of structures active on TRPV1

A dominant theme emerging from the analysis of vanilloid action is that every aspect shows great complexity. An implication, of course, is that this diversity provides extraordinary opportunities for pharmacological exploitation. One aspect of this diversity is the great variation in structures that bind to TRPV1 through the capsaicin RTX-recognition site. The standard concept of the structural features involved in binding is that presented in an elegant series of papers by Walpole et al. 5-7 ....