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

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• 作者：Ró ; bert Almá ; si ; É ; va Sző ; ke ; Kata B&#xf6 ; lcskei ; Angelika Varga ; Zsuzsanna Riedl ; Zoltá ; n Sá ; ndor ; Já ; nos Szolcsá ; nyi ; Gá ; bor Pethő
• 关键词：TRPV1 receptor ; 3-methyl-N-oleoyldopamine ; 4-methyl-N-oleoyldopamine ; N-oleoylethanolamide ; anandamide ; ⁴⁵Ca²⁺ uptake ; Ca²⁺ imaging ; Increasing-temperature (incremental) hot plate
• 刊名：Life Sciences
• 出版年：2008
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：12 March 2008
• 卷：82
• 期：11-12
• 页码：644-651
• 文件大小：723 K

摘要

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.