Actions of two naturally occurring saturated N‐acyldopamines on transient receptor potential vanilloid 1 (TRPV1) channels

Actions of two naturally occurring saturated N‐acyldopamines on transient receptor potential... Four long‐chain, linear fatty acid dopamides (N‐acyldopamines) have been identified in nervous bovine and rat tissues. Two unsaturated members of this family of lipids, N‐arachidonoyl‐dopamine (NADA) and N‐oleoyl‐dopamine, were shown to potently activate the transient receptor potential channel type V1 (TRPV1), also known as the vanilloid receptor type 1 for capsaicin. However, the other two congeners, N‐palmitoyl‐ and N‐stearoyl‐dopamine (PALDA and STEARDA), are inactive on TRPV1. We have investigated here the possibility that the two compounds act by enhancing the effect of NADA on TRPV1 (‘entourage’ effect). When pre‐incubated for 5 min with cells, both compounds dose‐dependently enhanced NADA's TRPV1‐mediated effect on intracellular Ca2+ in human embryonic kidney cells overexpressing the human TRPV1. In the presence of either PALDA or STEARDA (0.1–10 μM), the EC50 of NADA was lowered from ∼90 to ∼30 nM. The effect on intracellular Ca2+ by another endovanilloid, N‐arachidonoyl‐ethanolamine (anandamide, 50 nM), was also enhanced dose‐dependently by both PALDA and STEARDA. PALDA and STEARDA also acted in synergy with low pH (6.0–6.7) to enhance intracellular Ca2+ via TRPV1. When co‐injected with NADA (0.5 μg) in rat hind paws, STEARDA (5 μg) potentiated NADA's TRPV1‐mediated nociceptive effect by significantly shortening the withdrawal latencies from a radiant heat source. STEARDA (1 and 10 μg) also enhanced the nocifensive behavior induced by carrageenan in a typical test of inflammatory pain. These data indicate that, despite their inactivity per se on TRPV1, PALDA and STEARDA may play a role as ‘entourage’ compounds on chemicophysical agents that interact with these receptors, with possible implications in inflammatory and neuropathic pain. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Actions of two naturally occurring saturated N‐acyldopamines on transient receptor potential vanilloid 1 (TRPV1) channels

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Publisher
Wiley
Copyright
"Copyright © 2004 Wiley Subscription Services, Inc., A Wiley Company"
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0705924
pmid
15289293
Publisher site
See Article on Publisher Site

Abstract

Four long‐chain, linear fatty acid dopamides (N‐acyldopamines) have been identified in nervous bovine and rat tissues. Two unsaturated members of this family of lipids, N‐arachidonoyl‐dopamine (NADA) and N‐oleoyl‐dopamine, were shown to potently activate the transient receptor potential channel type V1 (TRPV1), also known as the vanilloid receptor type 1 for capsaicin. However, the other two congeners, N‐palmitoyl‐ and N‐stearoyl‐dopamine (PALDA and STEARDA), are inactive on TRPV1. We have investigated here the possibility that the two compounds act by enhancing the effect of NADA on TRPV1 (‘entourage’ effect). When pre‐incubated for 5 min with cells, both compounds dose‐dependently enhanced NADA's TRPV1‐mediated effect on intracellular Ca2+ in human embryonic kidney cells overexpressing the human TRPV1. In the presence of either PALDA or STEARDA (0.1–10 μM), the EC50 of NADA was lowered from ∼90 to ∼30 nM. The effect on intracellular Ca2+ by another endovanilloid, N‐arachidonoyl‐ethanolamine (anandamide, 50 nM), was also enhanced dose‐dependently by both PALDA and STEARDA. PALDA and STEARDA also acted in synergy with low pH (6.0–6.7) to enhance intracellular Ca2+ via TRPV1. When co‐injected with NADA (0.5 μg) in rat hind paws, STEARDA (5 μg) potentiated NADA's TRPV1‐mediated nociceptive effect by significantly shortening the withdrawal latencies from a radiant heat source. STEARDA (1 and 10 μg) also enhanced the nocifensive behavior induced by carrageenan in a typical test of inflammatory pain. These data indicate that, despite their inactivity per se on TRPV1, PALDA and STEARDA may play a role as ‘entourage’ compounds on chemicophysical agents that interact with these receptors, with possible implications in inflammatory and neuropathic pain.

Journal

British Journal of PharmacologyWiley

Published: Sep 1, 2004

Keywords: ; ; ; ; ; ; ; ; ;

References

  • Endovanilloid signaling in pain
    DI MARZO, V.; BLUMBERG, P.M.; SZALLASI, A.
  • The palmitoylethanolamide and oleamide enigmas: are these two fatty acid amides cannabimimetic
    LAMBERT, D.M.; DI MARZO, V.
  • Cannabimimetic activity, binding, and degradation of stearoylethanolamide within the mouse central nervous system
    MACCARRONE, M.; CARTONI, A.; PAROLARO, D.; MARGONELLI, A.; MASSI, P.; BARI, M.; BATTISTA, N.; FINAZZI‐AGRO', A.
  • The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1)
    SMART, D.; GUNTHORPE, M.J.; JERMAN, J.C.; NASIR, S.; GRAY, J.; MUIR, A.I.; CHAMBERS, J.K.; RANDALL, A.D.; DAVIS, J.B.

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