Direct Interaction of Adenosine with the TRPV1 Channel Protein

TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation

“…Several signaling pathways converge on TRPV1 to modulate its activity and, as shown in this and previous studies, alter neuron excitability (Bhave et al, 2003;Carr et al, 2003;Moriyama et al, 2003;Dai et al, 2004;Ferreira et al, 2004;Liu et al, 2004;Premkumar et al, 2004;Puntambekar et al, 2004). The potential role of TRPV1 in integrating different physical, chemical, and inflammatory signals and the comparatively high number of capsaicin-responsive colon sensory neurons support the relevance of this channel in sensation and visceral nociception.…”

Pharmacology of Vanilloid Transient Receptor Potential Cation Channels

“…Dynorphins, natural arginine-rich brain peptides that bind to -opioid receptors, are potent blockers of TRPV1, an activity that might contribute to their analgesic profile (Dessaint et al, 2004). Adenosine has also been proposed as an endogenous direct antagonist of TRPV1 (Puntambekar et al, 2004), whereas various dietary -3 fatty acids like eicosapentaenoic and linolenic acids inhibit TRPV1 and might be beneficial for the treatment of pain (Matta et al, 2007). More recently, the endogenous fatty acid amide hydrolase inhibitor N-arachidonoyl serotonin (25) has been shown to cause a direct block of TRPV1 (IC 50 ϳ40 nM) and to inhibit the generation of anandamide.…”

The Transient Receptor Potential Vanilloid-1 Channel in Thermoregulation: A Thermosensor It Is Not

“…Furthermore, several substances decrease the responsiveness of the TRPV1 channel to RTX and CAP. For instance, adenosine and its analogs interact with TRPV1, inhibit RTX binding, and inhibit CAP-induced inward currents in DRG neurons (Puntambekar et al, 2004), whereas calmodulin binds to the NH 2 -terminal region of the TRPV1 channel and inhibits gating to reduce the probability of channel opening (Rosenbaum et al, 2004). There is also evidence for a separate regulatory site (that binds several neuroleptic drugs), which can either increase or decrease vanilloid binding and the resulting calcium influx (Acs et al, 1995;Szallasi et al, 1996).…”