Spinal antinociception evoked by the triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene in mice: Evidence for the involvement of the glutamatergic system via NMDA and metabotropic gluta

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• 作者：Daniela Tagliari Longhi-Balbinot ; Evelise Fern ; es Pietrovski ; Vinicius Maria Gadotti ; Daniel Fern ; es Martins ; Valdir Alves Facundo ; Adair Roberto Soares Santos
• 关键词：Triterpene ; Antinociception ; Ionotropic glutamate receptor ; Metabotropic glutamate receptor
• 刊名：European Journal of Pharmacology
• 出版年：2009
• 出版时间：25 November 2009
• 年：2009
• 卷：623
• 期：1-3
• 页码：30-36
• 全文大小：866 K

文摘

The present study investigated the possible involvement of the glutamatergic and neurokinin systems in the antinociception caused by triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene (TTHL) in mice. TTHL given by intraperitoneal (i.p., 2.1 13;65.5 µmol/kg), intraplantar (i.pl., 6.5 13;65.5 nmol/paw) or intrathecal (i.t., 21.8 13;655 nmol/site) routes, produced dose-dependent inhibition of glutamate-induced nociception with ID₅₀ values of 12 µmol/kg; 34.2 nmol/paw; 233.8 nmol/site and inhibitions of 78 1; 6; 82 1; 4 and 77 1; 8 % , respectively. I.t. injection of TTHL (6.5 13;218 nmol/site, co-administered) also caused significant and dose-dependent reduction of nociceptive response induced by i.t. injection of glutamate (175 nmol/site), with ID₅₀ value of 54.5 nmol/site and inhibition of 51 1; 6 % . Moreover, TTHL (65.5 nmol/site) co-injected by i.t. route with agonist caused marked reduction of nociceptive responses induced by N-methyl-d-aspartate (NMDA, 450 pmol/site), (1;)-1-aminocyclopentane-trans-1,3 dicarboxylic acid (trans-ACPD, 10 nmol/site) and substance P (100 pmol/site), with inhibitions of 81 1; 7; 79 1; 7; 81 1; 11 % , respectively. Conversely, TTHL had no effect on ;1;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 135 pmol/site) and kainic acid (kainate, 110 pmol/site)-induced nociception. Moreover, the association of sub-effective doses of TTHL (6.5 nmol/site, i.t.) and MK-801(1 nmol/site, i.t.; non-competitive NMDA antagonist) or (RS)-MCPG (30 nmol/site, i.t.; non-selective group I/group II metabotropic glutamate receptor antagonist) produced a synergic antinociceptive effect in the nociception induced by NMDA or trans-ACPD, respectively. Together, these results provide experimental evidence for the involvement of the glutamatergic system (NMDA and metabotropic glutamate receptors) in the antinociceptive action caused by TTHL in mice.