Direct evidence for activation and desensitization of the capsaicin receptor by N-oleoyldopamine on TRPV1-transfected cell, line in gene deleted mice and in the rat

J. Szolcsányi, Z. Sándor, G. Pethő, A. Varga, K. Bölcskei, R. Almási, Z. Riedl, G. Hajós, G. Czéh

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Abstract

Effects of the endogenous lipid N-oleoyldopamine (OLDA) were analyzed on the rTRPV1-expressing HT1080 human fibrosarcoma cell line (HT5-1), on cultured rat trigeminal neurons, on the noxious heat threshold of rats and on nocifensive behavior of TRPV1 knockout mice. The EC50 of capsaicin and OLDA on 45Ca accumulation of rTRPV1-expressing HT5-1 cells was 36 nM and 1.8 μM, respectively. The efficacy of OLDA was 60% as compared to the maximum response of capsaicin. OLDA (330 nM to 3.3 μM) caused a transient increase in fluorescence of fura-2 loaded cultured small trigeminal neurons of the rat and rTRPV1-transfected HT5-1 cells measured with a ratiometric technique. Repeated application of OLDA and capsaicin caused similar desensitization in the Ca 2+ transients both in cultured neurons and rTRPV1-transfected HT5-1 cells. In the rat intraplantar injection of OLDA (5 nmol) decreased the noxious heat threshold by 6-9°C and this response was strongly inhibited by the TRPV1 antagonist iodoresiniferatoxin (0.05 nmol intraplantarly (i.pl.)). In wild-type mice OLDA (50 nmol i.pl.) evoked paw lifting/licking which was significantly less sustained in TRPV1 knockout mice. It is concluded that on TRPV1 capsaicin receptors OLDA is 50 times less potent than capsaicin and it might serve as an endogenous ligand for TRPV1 in the rat, but more likely in humans.

Original languageEnglish
Pages (from-to)155-158
Number of pages4
JournalNeuroscience Letters
Volume361
Issue number1-3
DOIs
Publication statusPublished - May 6 2004

Fingerprint

TRPV Cation Channels
Cell Line
Capsaicin
Genes
Neurons
Knockout Mice
Hot Temperature
N-oleoyldopamine
Psychologic Desensitization
Fura-2
Fibrosarcoma
Fluorescence
Ligands
Lipids
Injections

Keywords

  • Capsaicin
  • Endogenous ligand
  • N-Oleoyldopamine
  • Nociception
  • Thermal hyperalgesia
  • TRPV1
  • TRPV1 knockout mice
  • TRPV1-expressing cell line

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{31a5e6b6a6bf4fa385610f0083de9ad1,
title = "Direct evidence for activation and desensitization of the capsaicin receptor by N-oleoyldopamine on TRPV1-transfected cell, line in gene deleted mice and in the rat",
abstract = "Effects of the endogenous lipid N-oleoyldopamine (OLDA) were analyzed on the rTRPV1-expressing HT1080 human fibrosarcoma cell line (HT5-1), on cultured rat trigeminal neurons, on the noxious heat threshold of rats and on nocifensive behavior of TRPV1 knockout mice. The EC50 of capsaicin and OLDA on 45Ca accumulation of rTRPV1-expressing HT5-1 cells was 36 nM and 1.8 μM, respectively. The efficacy of OLDA was 60{\%} as compared to the maximum response of capsaicin. OLDA (330 nM to 3.3 μM) caused a transient increase in fluorescence of fura-2 loaded cultured small trigeminal neurons of the rat and rTRPV1-transfected HT5-1 cells measured with a ratiometric technique. Repeated application of OLDA and capsaicin caused similar desensitization in the Ca 2+ transients both in cultured neurons and rTRPV1-transfected HT5-1 cells. In the rat intraplantar injection of OLDA (5 nmol) decreased the noxious heat threshold by 6-9°C and this response was strongly inhibited by the TRPV1 antagonist iodoresiniferatoxin (0.05 nmol intraplantarly (i.pl.)). In wild-type mice OLDA (50 nmol i.pl.) evoked paw lifting/licking which was significantly less sustained in TRPV1 knockout mice. It is concluded that on TRPV1 capsaicin receptors OLDA is 50 times less potent than capsaicin and it might serve as an endogenous ligand for TRPV1 in the rat, but more likely in humans.",
keywords = "Capsaicin, Endogenous ligand, N-Oleoyldopamine, Nociception, Thermal hyperalgesia, TRPV1, TRPV1 knockout mice, TRPV1-expressing cell line",
author = "J. Szolcs{\'a}nyi and Z. S{\'a}ndor and G. Pethő and A. Varga and K. B{\"o}lcskei and R. Alm{\'a}si and Z. Riedl and G. Haj{\'o}s and G. Cz{\'e}h",
year = "2004",
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language = "English",
volume = "361",
pages = "155--158",
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TY - JOUR

T1 - Direct evidence for activation and desensitization of the capsaicin receptor by N-oleoyldopamine on TRPV1-transfected cell, line in gene deleted mice and in the rat

AU - Szolcsányi, J.

AU - Sándor, Z.

AU - Pethő, G.

AU - Varga, A.

AU - Bölcskei, K.

AU - Almási, R.

AU - Riedl, Z.

AU - Hajós, G.

AU - Czéh, G.

PY - 2004/5/6

Y1 - 2004/5/6

N2 - Effects of the endogenous lipid N-oleoyldopamine (OLDA) were analyzed on the rTRPV1-expressing HT1080 human fibrosarcoma cell line (HT5-1), on cultured rat trigeminal neurons, on the noxious heat threshold of rats and on nocifensive behavior of TRPV1 knockout mice. The EC50 of capsaicin and OLDA on 45Ca accumulation of rTRPV1-expressing HT5-1 cells was 36 nM and 1.8 μM, respectively. The efficacy of OLDA was 60% as compared to the maximum response of capsaicin. OLDA (330 nM to 3.3 μM) caused a transient increase in fluorescence of fura-2 loaded cultured small trigeminal neurons of the rat and rTRPV1-transfected HT5-1 cells measured with a ratiometric technique. Repeated application of OLDA and capsaicin caused similar desensitization in the Ca 2+ transients both in cultured neurons and rTRPV1-transfected HT5-1 cells. In the rat intraplantar injection of OLDA (5 nmol) decreased the noxious heat threshold by 6-9°C and this response was strongly inhibited by the TRPV1 antagonist iodoresiniferatoxin (0.05 nmol intraplantarly (i.pl.)). In wild-type mice OLDA (50 nmol i.pl.) evoked paw lifting/licking which was significantly less sustained in TRPV1 knockout mice. It is concluded that on TRPV1 capsaicin receptors OLDA is 50 times less potent than capsaicin and it might serve as an endogenous ligand for TRPV1 in the rat, but more likely in humans.

AB - Effects of the endogenous lipid N-oleoyldopamine (OLDA) were analyzed on the rTRPV1-expressing HT1080 human fibrosarcoma cell line (HT5-1), on cultured rat trigeminal neurons, on the noxious heat threshold of rats and on nocifensive behavior of TRPV1 knockout mice. The EC50 of capsaicin and OLDA on 45Ca accumulation of rTRPV1-expressing HT5-1 cells was 36 nM and 1.8 μM, respectively. The efficacy of OLDA was 60% as compared to the maximum response of capsaicin. OLDA (330 nM to 3.3 μM) caused a transient increase in fluorescence of fura-2 loaded cultured small trigeminal neurons of the rat and rTRPV1-transfected HT5-1 cells measured with a ratiometric technique. Repeated application of OLDA and capsaicin caused similar desensitization in the Ca 2+ transients both in cultured neurons and rTRPV1-transfected HT5-1 cells. In the rat intraplantar injection of OLDA (5 nmol) decreased the noxious heat threshold by 6-9°C and this response was strongly inhibited by the TRPV1 antagonist iodoresiniferatoxin (0.05 nmol intraplantarly (i.pl.)). In wild-type mice OLDA (50 nmol i.pl.) evoked paw lifting/licking which was significantly less sustained in TRPV1 knockout mice. It is concluded that on TRPV1 capsaicin receptors OLDA is 50 times less potent than capsaicin and it might serve as an endogenous ligand for TRPV1 in the rat, but more likely in humans.

KW - Capsaicin

KW - Endogenous ligand

KW - N-Oleoyldopamine

KW - Nociception

KW - Thermal hyperalgesia

KW - TRPV1

KW - TRPV1 knockout mice

KW - TRPV1-expressing cell line

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U2 - 10.1016/j.neulet.2003.12.025

DO - 10.1016/j.neulet.2003.12.025

M3 - Article

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VL - 361

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EP - 158

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

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