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 ISI 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 ISI Web of Science (80) Citing Articles via Google Scholar Google Scholar Articles by Tognetto, M. Articles by Bianchi, A. Search for Related Content PubMed PubMed Citation Articles by Tognetto, M. Articles by Bianchi, A.

 Previous Article  |  Next Article 

The Journal of Neuroscience, February 15, 2001, 21(4):1104-1109

Anandamide Excites Central Terminals of Dorsal Root Ganglion Neurons via Vanilloid Receptor-1 Activation

Michele Tognetto^{1, 3}, Silvia Amadesi¹, Selena Harrison¹, Christophe Creminon², Marcello Trevisani¹, Mirko Carreras¹, Mario Matera³, Pierangelo Geppetti¹, and Alfredo Bianchi³

¹ Headache Center, Departments of Experimental and Clinical Medicine and Neuroscience, University of Ferrara and Sant'Anna Hospital, 44100 Ferrara, Italy ² Le Commissariat à l'Énergie Atomique (CEA), Service de Pharmacologie et d'Immunologie, Département de Recherche Médicale, CEA-Saclay, 91191 Gif sur Yvette, France, and ³ Department of Pharmacology, University of Catania, 95123 Catania, Italy

Recently, the cannabinoid (CB) receptor agonist anandamide (AEA) has been shown to excite perivascular terminals of primary sensory neurons via activation of the vanilloid receptor-1 (VR-1). To determine whether AEA stimulates central terminals of these neurons, via VR-1 activation, we studied the release of calcitonin gene-related peptide (CGRP)- and substance P (SP)-like immunoreactivities (LI) from slices of rat dorsal spinal cord. Mobilization of Ca²⁺ in rat dorsal root ganglion (DRG) neurons in culture was also studied. AEA (0.1-10 µM) increased the outflow of CGRP-LI and SP-LI from slices of the rat dorsal spinal cord in a Ca²⁺-dependent manner and increased [Ca²⁺]_i in capsaicin-sensitive cultured DRG neurons. Both effects of AEA were abolished by capsaicin pretreatment and by the VR-1 antagonist capsazepine but not affected by the CB receptor antagonists AM281 or AM630. Both neuropeptide release and Ca²⁺ mobilization induced by electrical field stimulation (EFS) were inhibited by a low concentration of AEA (10 nM). Inhibition by AEA of EFS-induced responses was reversed by AM281 and AM630, but was not affected by capsazepine. Results indicate that stimulation of VR-1 with high concentrations of AEA excites central terminals of capsaicin-sensitive DRG neurons, thus causing neuropeptide release in the dorsal spinal cord. This novel activity opposes the CB receptor-mediated inhibitory action of low concentrations AEA. However, only if large amounts of endogenous AEA could be produced at the level of the dorsal spinal cord, they may not inhibit, but rather activate, nociceptive sensory neurons.

Key words: anandamide (AEA); calcium; calcitonin gene-related peptide (CGRP); capsaicin; sensory neurons; substance P; vanilloid receptor-1 (VR-1)

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/2141104-06$05.00/0

This article has been cited by other articles:

				C. S. Surowy, T. R. Neelands, B. R. Bianchi, S. McGaraughty, R. El Kouhen, P. Han, K. L. Chu, H. A. McDonald, M. Vos, W. Niforatos, et al. (R)-(5-tert-Butyl-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-4-yl)-urea (ABT-102) Blocks Polymodal Activation of Transient Receptor Potential Vanilloid 1 Receptors in Vitro and Heat-Evoked Firing of Spinal Dorsal Horn Neurons in Vivo J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 879 - 888. [Abstract] [Full Text] [PDF]

				Y. V. Medvedeva, M.-S. Kim, and Y. M. Usachev Mechanisms of Prolonged Presynaptic Ca2+ Signaling and Glutamate Release Induced by TRPV1 Activation in Rat Sensory Neurons J. Neurosci., May 14, 2008; 28(20): 5295 - 5311. [Abstract] [Full Text] [PDF]

				M. Trevisani, J. Siemens, S. Materazzi, D. M. Bautista, R. Nassini, B. Campi, N. Imamachi, E. Andre, R. Patacchini, G. S. Cottrell, et al. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1 PNAS, August 14, 2007; 104(33): 13519 - 13524. [Abstract] [Full Text] [PDF]

				E. Lizanecz, Z. Bagi, E. T. Pasztor, Z. Papp, I. Edes, N. Kedei, P. M. Blumberg, and A. Toth Phosphorylation-Dependent Desensitization by Anandamide of Vanilloid Receptor-1 (TRPV1) Function in Rat Skeletal Muscle Arterioles and in Chinese Hamster Ovary Cells Expressing TRPV1 Mol. Pharmacol., March 1, 2006; 69(3): 1015 - 1023. [Abstract] [Full Text] [PDF]

				N. R. Gavva, R. Tamir, Y. Qu, L. Klionsky, T. J. Zhang, D. Immke, J. Wang, D. Zhu, T. W. Vanderah, F. Porreca, et al. AMG 9810 [(E)-3-(4-t-Butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide], a Novel Vanilloid Receptor 1 (TRPV1) Antagonist with Antihyperalgesic Properties J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 474 - 484. [Abstract] [Full Text] [PDF]

				G. Appendino, L. De Petrocellis, M. Trevisani, A. Minassi, N. Daddario, A. S. Moriello, D. Gazzieri, A. Ligresti, B. Campi, G. Fontana, et al. Development of the First Ultra-Potent "Capsaicinoid" Agonist at Transient Receptor Potential Vanilloid Type 1 (TRPV1) Channels and Its Therapeutic Potential J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 561 - 570. [Abstract] [Full Text] [PDF]

				L. S. Premkumar, Z.-H. Qi, J. Van Buren, and M. Raisinghani Enhancement of Potency and Efficacy of NADA by PKC-Mediated Phosphorylation of Vanilloid Receptor J Neurophysiol, March 1, 2004; 91(3): 1442 - 1449. [Abstract] [Full Text] [PDF]

				T. F. FREUND, I. KATONA, and D. PIOMELLI Role of Endogenous Cannabinoids in Synaptic Signaling Physiol Rev, July 1, 2003; 83(3): 1017 - 1066. [Abstract] [Full Text] [PDF]

				S. M. Huang, T. Bisogno, M. Trevisani, A. Al-Hayani, L. De Petrocellis, F. Fezza, M. Tognetto, T. J. Petros, J. F. Krey, C. J. Chu, et al. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors PNAS, June 11, 2002; 99(12): 8400 - 8405. [Abstract] [Full Text] [PDF]

				A. C. Howlett, F. Barth, T. I. Bonner, G. Cabral, P. Casellas, W. A. Devane, C. C. Felder, M. Herkenham, K. Mackie, B. R. Martin, et al. International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors Pharmacol. Rev., June 1, 2002; 54(2): 161 - 202. [Abstract] [Full Text] [PDF]

				L. De Petrocellis, T. Bisogno, M. Maccarrone, J. B. Davis, A. Finazzi-Agro, and V. Di Marzo The Activity of Anandamide at Vanilloid VR1 Receptors Requires Facilitated Transport across the Cell Membrane and Is Limited by Intracellular Metabolism J. Biol. Chem., April 13, 2001; 276(16): 12856 - 12863. [Abstract] [Full Text] [PDF]

				Y. S. Lin and L.-Y. Lee Stimulation of pulmonary vagal C-fibres by anandamide in anaesthetized rats: role of vanilloid type 1 receptors J. Physiol., March 15, 2002; 539(3): 947 - 955. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help