View the Current Issue

Article

  • The EMBO Journal (2005) 24, 3026 - 3037
  • doi:10.1038/sj.emboj.7600784

Published online: 18 August 2005

Anandamide acts as an intracellular messenger amplifying Ca2+ influx via TRPV1 channels

Mario van der Stelt1,a, Marcello Trevisani2, Vittorio Vellani3,4, Luciano De Petrocellis5, Aniello Schiano Moriello1,5, Barbara Campi2, Peter McNaughton4, Piero Geppetti2 and Vincenzo Di Marzo1

  1. Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy
  2. Department of Experimental Medicine and Clinical Medicine, Pharmacology Unit, University of Ferrara, Ferrara, Italy
  3. Dipartimento di Scienze Biomediche, Universita' di Modena e Reggio Emilia, Modena, Italy
  4. Department of Pharmacology, University of Cambridge, Cambridge, UK
  5. Istitute of Cibernetica Eduardo Caianiello, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy

Correspondence to:

Vincenzo Di Marzo, Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy. Tel.: +39 081 8675093; Fax: +39 081 8041770; E-mail: vdimarzo@icmib.na.cnr.it

aPresent address: NV Organon, PO Box 20, 5340 BH Oss, The Netherlands

Received 30 March 2005; Accepted 21 July 2005

The endocannabinoid anandamide is able to interact with the transient receptor potential vanilloid 1 (TRPV1) channels at a molecular level. As yet, endogenously produced anandamide has not been shown to activate TRPV1, but this is of importance to understand the physiological function of this interaction. Here, we show that intracellular Ca2+ mobilization via the purinergic receptor agonist ATP, the muscarinic receptor agonist carbachol or the Ca2+-ATPase inhibitor thapsigargin leads to formation of anandamide, and subsequent TRPV1-dependent Ca2+ influx in transfected cells and sensory neurons of rat dorsal root ganglia (DRG). Anandamide metabolism and efflux from the cell tonically limit TRPV1-mediated Ca2+ entry. In DRG neurons, this mechanism was found to lead to TRPV1-mediated currents that were enhanced by selective blockade of anandamide cellular efflux. Thus, endogenous anandamide is formed on stimulation of metabotropic receptors coupled to the phospholipase C/inositol 1,4,5-triphosphate pathway and then signals to TRPV1 channels. This novel intracellular function of anandamide may precede its action at cannabinoid receptors, and might be relevant to its control over neurotransmitter release.

  • Keywords:

    • anandamide,
    • Ca2+ homeostasis,
    • metabotropic,
    • store depletion,
    • vanilloid