A role for the anandamide membrane transporter in TRPV1-mediated neurosecretion from trigeminal sensory neurons

Theodore J. Price, Amol M Patwardhan, Christopher M. Flores, Kenneth M. Hargreaves

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Many n-acylethanolamines utilize the anandamide membrane transporter (AMT) to gain facilitated access to the intracellular compartment, hence, we hypothesized that this mechanism might be important for anandamide (AEA)- and N-arachidonoyl-dopamine (NADA)-evoked CGRP release from cultured trigeminal ganglion (TG) neurons. Using [14C]AEA we demonstrated that TG neurons transported AEA in a FAAH- and AMT-inhibitable fashion. Although TRPV1-positive TG neurons were found to express fatty acid amide hydrolase, the application of FAAH inhibitors had no effect on AEA-evoked CGRP release. In contrast, application of the AMT inhibitors OMDM-2 or VDM-11 significantly reduced the potency and efficacy of AEA-, NADA- and capsaicin-evoked CGRP release. Moreover OMDM-2 (IC50 values ranging from 6.4-9.6 μM) and VDM-11 (IC 50 values ranging from 5.3-11 μM) inhibited CGRP release evoked by EC80 concentrations of AEA, NADA and CAP and these values were consistent with IC50s obtained for inhibition of uptake. OMDM-2 had no effect on CGRP release per se while VDM-11 evoked CGRP release on its own (EC50 ∼ 35 μM) in a CPZ-insensitive, but ruthenium red (RR)-sensitive fashion. This is the first demonstration that TG sensory neurons possess an AMT-like mechanism suggesting that this mechanism is important for the pharmacological action of AEA and NADA at native TRPV1 channels.

Original languageEnglish (US)
Pages (from-to)25-39
Number of pages15
JournalNeuropharmacology
Volume49
Issue number1
DOIs
StatePublished - Jul 2005
Externally publishedYes

Fingerprint

Neurosecretion
Membrane Transport Proteins
Sensory Receptor Cells
Trigeminal Ganglion
Dopamine
Neurons
Ruthenium Red
Capsaicin
Inhibitory Concentration 50
anandamide
Pharmacology

Keywords

  • Anandamide membrane transport
  • Cannabinoid
  • Neuropeptide release
  • Pain
  • Sensory neuron
  • Vanilloid

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

A role for the anandamide membrane transporter in TRPV1-mediated neurosecretion from trigeminal sensory neurons. / Price, Theodore J.; Patwardhan, Amol M; Flores, Christopher M.; Hargreaves, Kenneth M.

In: Neuropharmacology, Vol. 49, No. 1, 07.2005, p. 25-39.

Research output: Contribution to journalArticle

Price, Theodore J. ; Patwardhan, Amol M ; Flores, Christopher M. ; Hargreaves, Kenneth M. / A role for the anandamide membrane transporter in TRPV1-mediated neurosecretion from trigeminal sensory neurons. In: Neuropharmacology. 2005 ; Vol. 49, No. 1. pp. 25-39.
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