QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (58) Citing Articles via Google Scholar Google Scholar Articles by Liu, L. Articles by Simon, S. A. Search for Related Content PubMed PubMed Citation Articles by Liu, L. Articles by Simon, S. A.

 Previous Article  |  Next Article 

Volume 17, Number 11, Issue of June 1, 1997 pp. 4101-4111
Copyright ©1997 Society for Neuroscience

The Responses of Rat Trigeminal Ganglion Neurons to Capsaicin and Two Nonpungent Vanilloid Receptor Agonists, Olvanil and Glyceryl Nonamide

Received Dec. 20, 1996; revised March 4, 1997; accepted March 24, 1997.

L. Liu¹, Y.-C. Lo², I.-J. Chen¹, and S. A. Simon¹

¹ Departments of Neurobiology and Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710 and ² Department of Pharmacology, Kaohsiung, Taiwan, 80708 Republic of China

Capsaicin, the pungent ingredient in hot pepper, activates and subsequently desensitizes a subset of polymodal nociceptors. Because its initial application to skin produces pain, nonpungent analogs such as olvanil and glyceryl nonivamide (GLNVA) were synthesized to enhance its clinical use. To explore how these nonpungent analogs differ from capsaicin, whole-cell patch-clamp recordings were performed on cultured rat trigeminal ganglion neurons.

In neurons held at 60 mV, capsaicin, olvanil, and GLNVA were found to activate one or two kinetically distinct inward currents. Two inward currents were also activated when extracellular Ca²⁺ was replaced with Ba²⁺ and also when intracellular chloride was replaced by aspartate. The reversal potentials of the rapidly and slowly activating currents were 15.3 ± 6 and 4.0 ± 2.5 mV, respectively. These data provide strong evidence for subtypes of vanilloid receptors. One difference among these agonists is that, on average, the activation kinetics of the currents evoked by 1 µM olvanil and 30 µM GLNVA are considerably slower than those evoked by 1 µM capsaicin. Measurements of the peak current, Ip, versus agonist concentration were fit to the Hill equation to yield values of the half maximal concentrations (K_1/2), and the Hill coefficients (n). For capsaicin, olvanil, and GLNVA, K_1/2 = 0.68, 0.59, and 27.0 µM; and n = 1.38, 1.32, and 1.24, respectively.

We propose that olvanil and GLNVA are nonpungent because they activate different subtypes of receptors and/or because of their activation kinetics (compared with capsaicin) are, on average, slower than the rate they inhibit action potentials from polymodal nociceptors.

Key words: pain; taste; vanilloid receptors; pungent; olvanil; capsaicin

This article has been cited by other articles:

				A. N. Akopian, N. B. Ruparel, A. Patwardhan, and K. M. Hargreaves Cannabinoids Desensitize Capsaicin and Mustard Oil Responses in Sensory Neurons via TRPA1 Activation J. Neurosci., January 30, 2008; 28(5): 1064 - 1075. [Abstract] [Full Text] [PDF]

				Y.-C. Lin, H.-W. Uang, R.-J. Lin, I.-J. Chen, and Y.-C. Lo Neuroprotective Effects of Glyceryl Nonivamide against Microglia-Like Cells and 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Human Dopaminergic Neuroblastoma Cells J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 877 - 887. [Abstract] [Full Text] [PDF]

				H. Xu, W. Tian, Y. Fu, T. T. Oyama, S. Anderson, and D. M. Cohen Functional effects of nonsynonymous polymorphisms in the human TRPV1 gene Am J Physiol Renal Physiol, December 1, 2007; 293(6): F1865 - F1876. [Abstract] [Full Text] [PDF]

				A. N. Akopian, N. B. Ruparel, N. A. Jeske, and K. M. Hargreaves Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization J. Physiol., August 15, 2007; 583(1): 175 - 193. [Abstract] [Full Text] [PDF]

				J. A. Matta, R. L. Miyares, and G. P. Ahern TRPV1 is a novel target for omega-3 polyunsaturated fatty acids J. Physiol., January 15, 2007; 578(2): 397 - 411. [Abstract] [Full Text] [PDF]

				A. M. Patwardhan, N. A. Jeske, T. J. Price, N. Gamper, A. N. Akopian, and K. M. Hargreaves The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin PNAS, July 25, 2006; 103(30): 11393 - 11398. [Abstract] [Full Text] [PDF]

				J. Lazar, D. C. Braun, A. Toth, Y. Wang, L. V. Pearce, V. A. Pavlyukovets, P. M. Blumberg, S. H. Garfield, S. Wincovitch, H.-K. Choi, et al. Kinetics of Penetration Influence the Apparent Potency of Vanilloids on TRPV1 Mol. Pharmacol., April 1, 2006; 69(4): 1166 - 1173. [Abstract] [Full Text] [PDF]

				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. TRPV1 Recapitulates Native Capsaicin Receptor in Sensory Neurons in Association with Fas-Associated Factor 1 J. Neurosci., March 1, 2006; 26(9): 2403 - 2412. [Abstract] [Full Text] [PDF]

				Y. Wang, A. Toth, R. Tran, T. Szabo, J. D. Welter, P. M. Blumberg, J. Lee, S.-U. Kang, J.-O. Lim, and J. Lee High-Affinity Partial Agonists of the Vanilloid Receptor Mol. Pharmacol., August 1, 2003; 64(2): 325 - 333. [Abstract] [Full Text] [PDF]

				P. Wahl, C. Foged, S. Tullin, and C. Thomsen Iodo-Resiniferatoxin, a New Potent Vanilloid Receptor Antagonist Mol. Pharmacol., January 1, 2001; 59(1): 9 - 15. [Abstract] [Full Text]

				S. Schwarz, W. Greffrath, D. Busselberg, and R.-D. Treede Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats J. Physiol., November 1, 2000; 528(3): 539 - 549. [Abstract] [Full Text] [PDF]

				M. PADILLA, G. T. CLARK, and R. L. MERRILL TOPICAL MEDICATIONS FOR OROFACIAL NEUROPATHIC PAIN: A REVIEW J Am Dent Assoc, February 1, 2000; 131(2): 184 - 195. [Abstract] [Full Text] [PDF]

				T. Kirschstein, W. Greffrath, D. Busselberg, and R.-D. Treede Inhibition of Rapid Heat Responses in Nociceptive Primary Sensory Neurons of Rats by Vanilloid Receptor Antagonists J Neurophysiol, December 1, 1999; 82(6): 2853 - 2860. [Abstract] [Full Text] [PDF]

				A S Piper, J C Yeats, S Bevan, and R J Docherty A study of the voltage dependence of capsaicin-activated membrane currents in rat sensory neurones before and after acute desensitization J. Physiol., August 1, 1999; 518(3): 721 - 733. [Abstract] [Full Text] [PDF]

				A. Szallasi and P. M. Blumberg Vanilloid (Capsaicin) Receptors and Mechanisms Pharmacol. Rev., June 1, 1999; 51(2): 159 - 212. [Abstract] [Full Text] [PDF]

				E. Carstens, N. Kuenzler, and H. O. Handwerker Activation of Neurons in Rat Trigeminal Subnucleus Caudalis by Different Irritant Chemicals Applied to Oral or Ocular Mucosa J Neurophysiol, August 1, 1998; 80(2): 465 - 492. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help