Anandamide produced by Ca2+-insensitive enzymes induces excitation in primary sensory neurons

Angelika Varga, Agnes Jenes, Timothy H. Marczylo, Joao Sousa-Valente, Jie Chen, Jonothan Austin, Srikumaran Selvarajah, Fabiana Piscitelli, Anna P. Andreou, Anthony H. Taylor, Fiona Kyle, Mohammed Yaqoob, Sue Brain, John P M White, L. Csernoch, Vincenzo Di Marzo, Laki Buluwela, I. Nagy

Research output: Article

6 Citations (Scopus)

Abstract

The endogenous lipid agent N-arachidonoylethanolamine (anandamide), among other effects, has been shown to be involved in nociceptive processing both in the central and peripheral nervous systems. Anandamide is thought to be synthesised by several enzymatic pathways both in a Ca2+-sensitive and Ca2+-insensitive manner, and rat primary sensory neurons produce anandamide. Here, we show for the first time, that cultured rat primary sensory neurons express at least four of the five known Ca2+-insensitive enzymes implicated in the synthesis of anandamide, and that application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl, the common substrate of the anandamide-synthesising pathways, results in anandamide production which is not changed by the removal of extracellular Ca2+. We also show that anandamide, which has been synthesised in primary sensory neurons following the application of 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine-N-arachidonoyl induces a transient receptor potential vanilloid type 1 ion channel-mediated excitatory effect that is not inhibited by concomitant activation of the cannabinoid type 1 receptor. Finally, we show that sub-populations of transient receptor potential vanilloid type 1 ion channel-expressing primary sensory neurons also express some of the putative Ca2+-insensitive anandamide-synthesising enzymes. Together, these findings indicate that anandamide synthesised by primary sensory neuron via a Ca2+-insensitive manner has an excitatory rather than an inhibitory role in primary sensory neurons and that excitation is mediated predominantly through autocrine signalling. Regulation of the activity of the Ca 2+-insensitive anandamide-synthesising enzymes in these neurons may be capable of regulating the activity of these cells, with potential relevance to controlling nociceptive processing.

Original languageEnglish
Pages (from-to)1421-1435
Number of pages15
JournalPflugers Archiv European Journal of Physiology
Volume466
Issue number7
DOIs
Publication statusPublished - 2014

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Sensory Receptor Cells
Neurons
Enzymes
Ion Channels
Rats
Autocrine Communication
anandamide
Cannabinoid Receptors
Cannabinoids
Peripheral Nervous System
Neurology
Processing
Central Nervous System
Chemical activation
Cells
Lipids

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)
  • Medicine(all)

Cite this

Anandamide produced by Ca2+-insensitive enzymes induces excitation in primary sensory neurons. / Varga, Angelika; Jenes, Agnes; Marczylo, Timothy H.; Sousa-Valente, Joao; Chen, Jie; Austin, Jonothan; Selvarajah, Srikumaran; Piscitelli, Fabiana; Andreou, Anna P.; Taylor, Anthony H.; Kyle, Fiona; Yaqoob, Mohammed; Brain, Sue; White, John P M; Csernoch, L.; Di Marzo, Vincenzo; Buluwela, Laki; Nagy, I.

In: Pflugers Archiv European Journal of Physiology, Vol. 466, No. 7, 2014, p. 1421-1435.

Research output: Article

Varga, A, Jenes, A, Marczylo, TH, Sousa-Valente, J, Chen, J, Austin, J, Selvarajah, S, Piscitelli, F, Andreou, AP, Taylor, AH, Kyle, F, Yaqoob, M, Brain, S, White, JPM, Csernoch, L, Di Marzo, V, Buluwela, L & Nagy, I 2014, 'Anandamide produced by Ca2+-insensitive enzymes induces excitation in primary sensory neurons', Pflugers Archiv European Journal of Physiology, vol. 466, no. 7, pp. 1421-1435. https://doi.org/10.1007/s00424-013-1360-7
Varga, Angelika ; Jenes, Agnes ; Marczylo, Timothy H. ; Sousa-Valente, Joao ; Chen, Jie ; Austin, Jonothan ; Selvarajah, Srikumaran ; Piscitelli, Fabiana ; Andreou, Anna P. ; Taylor, Anthony H. ; Kyle, Fiona ; Yaqoob, Mohammed ; Brain, Sue ; White, John P M ; Csernoch, L. ; Di Marzo, Vincenzo ; Buluwela, Laki ; Nagy, I. / Anandamide produced by Ca2+-insensitive enzymes induces excitation in primary sensory neurons. In: Pflugers Archiv European Journal of Physiology. 2014 ; Vol. 466, No. 7. pp. 1421-1435.
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AU - Austin, Jonothan

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AU - Yaqoob, Mohammed

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