Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

J. Neurosci. 20 (22): 8298-8304

Copyright © 2000 by the Society for Neuroscience.

The Journal of Neuroscience, November 15, 2000, 20(22):8298-8304

Intracellular ATP Increases Capsaicin-Activated Channel Activity by Interacting with Nucleotide-Binding Domains

Jiyeon Kwak1, Myeong Hyeon Wang1, Sun Wook Hwang1, Tae-Yoon Kim2, Soon-Youl Lee1, and Uhtaek Oh1

1 Sensory Research Group, Creative Research Initiatives, Seoul National University, College of Pharmacy, Kwanak, Shinlim San 56-1, Seoul 151-742, Korea, and 2 Department of Immunology and Dermatology, College of Medicine, Catholic University, Seoul 137-040, Korea

Capsaicin (CAP)-activated ion channel plays a key role in generating nociceptive neural signals in sensory neurons. Here we present evidence that intracellular ATP upregulates the activity of capsaicin receptor channel. In inside-out membrane patches isolated from sensory neurons, application of CAP activated a nonselective cation channel (icap). Further addition of ATP to the bath caused a significant increase in icap, with a K1/2 of 3.3 mM. Nonhydrolyzable analogs of ATP, adenylimidodiphosphate and adenosine 5'-O-(3-thio)-triphosphate, also increased icap. Neither Mg2+-free medium nor inhibitors of various kinases blocked the increase in icap induced by ATP. The enhancing effect of ATP was also observed in inside-out patches of oocytes expressing vanilloid receptor 1, a cloned capsaicin receptor. Single point mutations (D178N, K735R) within the putative Walker type nucleotide-binding domains abolished the effect of ATP. These results show that ATP increases icap in sensory neurons by direct interaction with the CAP channel without involvement of phosphorylation.

Key words: capsaicin receptor; VR1; ATP; allosteric regulation; nucleotide-binding motif; pain

Copyright © 2000 Society for Neuroscience  0270-6474/00/20228298-07$05.00/0

Promiscuous Activation of Transient Receptor Potential Vanilloid 1 (TRPV1) Channels by Negatively Charged Intracellular Lipids: THE KEY ROLE OF ENDOGENOUS PHOSPHOINOSITIDES IN MAINTAINING CHANNEL ACTIVITY.
V. Lukacs, J.-M. Rives, X. Sun, E. Zakharian, and T. Rohacs (2013)
J. Biol. Chem. 288, 35003-35013
   Abstract »    Full Text »    PDF »
Cell-Permeable, Small-Molecule Activators of the Insulin-Degrading Enzyme.
S. S. Kukday, S. P. Manandhar, M. C. Ludley, M. E. Burriss, B. J. Alper, and W. K. Schmidt (2012)
J Biomol Screen 17, 1348-1361
   Abstract »    Full Text »    PDF »
Intracellular acidification evoked by moderate extracellular acidosis attenuates transient receptor potential V1 (TRPV1) channel activity in rat dorsal root ganglion neurons.
S. Chung, Y.-H. Kim, J.-Y. Koh, T.-S. Nam, and D.-S. Ahn (2011)
Exp Physiol 96, 1270-1281
   Abstract »    Full Text »    PDF »
C-terminal Dimerization Activates the Nociceptive Transduction Channel Transient Receptor Potential Vanilloid 1.
S. Wang and H.-h. Chuang (2011)
J. Biol. Chem. 286, 40601-40607
   Abstract »    Full Text »    PDF »
Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5)P2.
E. Zakharian, C. Cao, and T. Rohacs (2011)
FASEB J 25, 3915-3928
   Abstract »    Full Text »    PDF »
Ca2+-Dependent Desensitization of TRPV2 Channels Is Mediated by Hydrolysis of Phosphatidylinositol 4,5-Bisphosphate.
J. Mercado, A. Gordon-Shaag, W. N. Zagotta, and S. E. Gordon (2010)
J. Neurosci. 30, 13338-13347
   Abstract »    Full Text »    PDF »
Effect of Nicotine on Chorda Tympani Responses to Salty and Sour Stimuli.
V. Lyall, T.-H. T. Phan, S. Mummalaneni, M. Mansouri, G. L. Heck, G. Kobal, and J. A. DeSimone (2007)
J Neurophysiol 98, 1662-1674
   Abstract »    Full Text »    PDF »
TRPV1 Recapitulates Native Capsaicin Receptor in Sensory Neurons in Association with Fas-Associated Factor 1.
S. Kim, C. Kang, C. Y. Shin, S. W. Hwang, Y. D. Yang, W. S. Shim, M.-Y. Park, E. Kim, M. Kim, B.-M. Kim, et al. (2006)
J. Neurosci. 26, 2403-2412
   Abstract »    Full Text »    PDF »
Inhibitory modulation of distal C-terminal on protein kinase C-dependent phospho-regulation of rat TRPV1 receptors.
B. Liu, W. Ma, S. Ryu, and F. Qin (2004)
J. Physiol. 560, 627-638
   Abstract »    Full Text »    PDF »
Capsaicin Potentiates Wild-Type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator Chloride-Channel Currents.
T. Ai, S. G. Bompadre, X. Wang, S. Hu, M. Li, and T.-C. Hwang (2004)
Mol. Pharmacol. 65, 1415-1426
   Abstract »    Full Text »    PDF »
Nicotine Inhibits Voltage-Dependent Sodium Channels and Sensitizes Vanilloid Receptors.
L. Liu, W. Zhu, Z.-S. Zhang, T. Yang, A. Grant, G. Oxford, and S. A. Simon (2004)
J Neurophysiol 91, 1482-1491
   Abstract »    Full Text »    PDF »
Enhancement of Potency and Efficacy of NADA by PKC-Mediated Phosphorylation of Vanilloid Receptor.
L. S. Premkumar, Z.-H. Qi, J. Van Buren, and M. Raisinghani (2004)
J Neurophysiol 91, 1442-1449
   Abstract »    Full Text »    PDF »
Functional Role of C-Terminal Cytoplasmic Tail of Rat Vanilloid Receptor 1.
V. Vlachova, J. Teisinger, K. Susankova, A. Lyfenko, R. Ettrich, and L. Vyklicky (2003)
J. Neurosci. 23, 1340-1350
   Abstract »    Full Text »    PDF »
Single-channel properties of native and cloned rat vanilloid receptors.
L. S Premkumar, S. Agarwal, and D. Steffen (2002)
J. Physiol. 545, 107-117
   Abstract »    Full Text »    PDF »
High Affinity Antagonists of the Vanilloid Receptor.
Y. Wang, T. Szabo, J. D. Welter, A. Toth, R. Tran, J. Lee, S. U. Kang, Y.-G. Suh, P. M. Blumberg, and J. Lee (2002)
Mol. Pharmacol. 62, 947-956
   Abstract »    Full Text »    PDF »
Bradykinin Lowers the Threshold Temperature for Heat Activation of Vanilloid Receptor 1.
T. Sugiura, M. Tominaga, H. Katsuya, and K. Mizumura (2002)
J Neurophysiol 88, 544-548
   Abstract »    Full Text »    PDF »
Interaction between vanilloid receptors and purinergic metabotropic receptors: Pain perception and beyond.
L. S. Premkumar (2001)
PNAS 98, 6537-6539
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882