Actions of 3-methyl-N-oleoyldopamine, 4-methyl-N-oleoyldopamine and N-oleoylethanolamide on the rat TRPV1 receptor in vitro and in vivo

Róbert Almási, E. Szöke, K. Bölcskei, Angelika Varga, Z. Riedl, Zoltán Sándor, J. Szolcsányi, G. Pethő

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

N-oleoyldopamine (OLDA) has been identified as an agonist of the transient receptor potential vanilloid type 1 (TRPV1) receptor. A related fatty acid amide, N-oleoylethanolamide (OEA), was found to excite sensory neurons and produce visceral hyperalgesia via activation of the TRPV1 receptor, however, a recent study described this agent as an antinociceptive one. The aim of the present paper was to characterize two newly synthesized derivatives of N-oleoyldopamine, 3-methyl-N-oleoyldopamine (3-MOLDA) and 4-methyl-N-oleoyldopamine (4-MOLDA) as well as OEA with regard to their effects on the TRPV1 receptor. Radioactive 45Ca2+ uptake was measured in HT5-1 cells transfected with the rat TRPV1 receptor and intracellular Ca2+ concentration was monitored by fura-2 microfluorimetry in cultured trigeminal sensory neurons. Thermonociception was assessed by determining the behavioral noxious heat threshold in rats. 3-MOLDA induced 45Ca2+ uptake in a concentration-dependent manner, whereas 4-MOLDA and OEA were without effect. 4-MOLDA and OEA, however, concentration-dependently reduced the 45Ca2+ uptake-inducing effect of capsaicin. In trigeminal sensory neurons, 3-MOLDA caused an increase in intracellular Ca2+ concentration and this effect exhibited tachyphylaxis upon repeated application. Again, 4-MOLDA and OEA failed to alter intracellular Ca2+ levels. Upon intraplantar injection, 3-MOLDA caused an 8-10 °C drop of the noxious heat threshold in rats which was inhibited by the TRPV1 receptor antagonist iodo-resiniferatoxin. 4-MOLDA and OEA failed to alter the heat threshold but inhibited the threshold drop induced by the TRPV1 receptor agonist resiniferatoxin. These data show that 3-MOLDA behaves as an agonist, whereas 4-MOLDA and OEA appear to be antagonists, at the rat TRPV1 receptor.

Original languageEnglish
Pages (from-to)644-651
Number of pages8
JournalLife Sciences
Volume82
Issue number11-12
DOIs
Publication statusPublished - Mar 12 2008

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Rats
Sensory Receptor Cells
Neurons
Hot Temperature
Cytophotometry
Tachyphylaxis
Capsaicin
Hyperalgesia
oleoylethanolamide
3-methyl-N-oleoyldopamine
vanilloid receptor subtype 1
4-methyl-N-oleoyldopamine
In Vitro Techniques
Amides
Analgesics
Fatty Acids
Chemical activation
Derivatives
Injections

Keywords

  • 3-methyl-N-oleoyldopamine
  • 4-methyl-N-oleoyldopamine
  • Ca uptake
  • anandamide
  • Ca imaging
  • Increasing-temperature (incremental) hot plate
  • N-oleoylethanolamide
  • TRPV1 receptor

ASJC Scopus subject areas

  • Pharmacology

Cite this

Actions of 3-methyl-N-oleoyldopamine, 4-methyl-N-oleoyldopamine and N-oleoylethanolamide on the rat TRPV1 receptor in vitro and in vivo. / Almási, Róbert; Szöke, E.; Bölcskei, K.; Varga, Angelika; Riedl, Z.; Sándor, Zoltán; Szolcsányi, J.; Pethő, G.

In: Life Sciences, Vol. 82, No. 11-12, 12.03.2008, p. 644-651.

Research output: Contribution to journalArticle

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AU - Bölcskei, K.

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