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Contribution of spinal glutamatergic receptors to the antinociception caused by agmatine in mice.
Brain Res. 2006 Jun 06; 1093(1):116-22.BR

Abstract

This study was designed to evaluate the role of spinal glutamatergic receptors in the antinociception elicited by agmatine in mice. Intraperitoneal (i.p.) administration of agmatine (1.0-100.0 mg/kg) dose dependently inhibited the nociceptive response induced by intrathecal (i.t.) injection of glutamate, N-methy-D-aspartate (NMDA) and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), with mean ID(50) values of 16.7, 6.8 and 27.0 mg/kg, respectively. However, agmatine completely failed to affect the nociception induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainic acid (kainate). Agmatine injected by i.t. route (10-100 microg/site) also produced dose-related inhibition of NMDA- and trans-ACPD-induced biting response with mean ID(50) values of 29.6 and 36.0 mug/site, respectively. The nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (l-NOARG) (75.0 mg/kg, i.p.) also consistently inhibited glutamate-, NMDA- and trans-ACPD-induced nociception (41 +/- 13, 100 and 83 +/- 6%, of inhibition, respectively) but had no effect on the same response caused by AMPA and kainate agonists. The selective NMDA receptor antagonist (5S,10R)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d] (MK-801) at a low dose (0.05 mg/kg, i.p.) inhibited the nociceptive response caused by both glutamate and NMDA agonists (inhibitions of 35 +/- 1 and 72 +/- 2%, respectively). At a high dose, MK-801 (0.5 mg/kg, i.p.) significantly inhibited the biting response induced by i.t. administration of all the glutamatergic agonists tested: glutamate, AMPA, NMDA, kainate and trans-ACPD, with inhibitions of 49 +/- 8, 84 +/- 16, 84 +/- 3, 76 +/- 8 and 97 +/- 2%, respectively. Together, these results provide experimental evidence indicating that agmatine given systemically and spinally produce marked antinociception at spinal sites in mice. Furthermore, an interaction with glutamate receptors, namely NMDA and trans-ACPD, metabotropic and NMDA-ionotropic origin, by a mechanism similar to that of nitric oxide (NO) inhibitors, seems to account for the agmatine antinociceptive action.

Authors+Show Affiliations

Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-900, SC, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16765330

Citation

Gadotti, Vinicius M., et al. "Contribution of Spinal Glutamatergic Receptors to the Antinociception Caused By Agmatine in Mice." Brain Research, vol. 1093, no. 1, 2006, pp. 116-22.
Gadotti VM, Tibola D, Paszcuk AF, et al. Contribution of spinal glutamatergic receptors to the antinociception caused by agmatine in mice. Brain Res. 2006;1093(1):116-22.
Gadotti, V. M., Tibola, D., Paszcuk, A. F., Rodrigues, A. L., Calixto, J. B., & Santos, A. R. (2006). Contribution of spinal glutamatergic receptors to the antinociception caused by agmatine in mice. Brain Research, 1093(1), 116-22.
Gadotti VM, et al. Contribution of Spinal Glutamatergic Receptors to the Antinociception Caused By Agmatine in Mice. Brain Res. 2006 Jun 6;1093(1):116-22. PubMed PMID: 16765330.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contribution of spinal glutamatergic receptors to the antinociception caused by agmatine in mice. AU - Gadotti,Vinicius M, AU - Tibola,Daiane, AU - Paszcuk,Ana Flavia, AU - Rodrigues,Ana Lúcia S, AU - Calixto,João B, AU - Santos,Adair R S, Y1 - 2006/06/12/ PY - 2005/11/04/received PY - 2006/03/20/revised PY - 2006/03/22/accepted PY - 2006/6/13/pubmed PY - 2006/9/13/medline PY - 2006/6/13/entrez SP - 116 EP - 22 JF - Brain research JO - Brain Res VL - 1093 IS - 1 N2 - This study was designed to evaluate the role of spinal glutamatergic receptors in the antinociception elicited by agmatine in mice. Intraperitoneal (i.p.) administration of agmatine (1.0-100.0 mg/kg) dose dependently inhibited the nociceptive response induced by intrathecal (i.t.) injection of glutamate, N-methy-D-aspartate (NMDA) and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), with mean ID(50) values of 16.7, 6.8 and 27.0 mg/kg, respectively. However, agmatine completely failed to affect the nociception induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainic acid (kainate). Agmatine injected by i.t. route (10-100 microg/site) also produced dose-related inhibition of NMDA- and trans-ACPD-induced biting response with mean ID(50) values of 29.6 and 36.0 mug/site, respectively. The nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (l-NOARG) (75.0 mg/kg, i.p.) also consistently inhibited glutamate-, NMDA- and trans-ACPD-induced nociception (41 +/- 13, 100 and 83 +/- 6%, of inhibition, respectively) but had no effect on the same response caused by AMPA and kainate agonists. The selective NMDA receptor antagonist (5S,10R)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d] (MK-801) at a low dose (0.05 mg/kg, i.p.) inhibited the nociceptive response caused by both glutamate and NMDA agonists (inhibitions of 35 +/- 1 and 72 +/- 2%, respectively). At a high dose, MK-801 (0.5 mg/kg, i.p.) significantly inhibited the biting response induced by i.t. administration of all the glutamatergic agonists tested: glutamate, AMPA, NMDA, kainate and trans-ACPD, with inhibitions of 49 +/- 8, 84 +/- 16, 84 +/- 3, 76 +/- 8 and 97 +/- 2%, respectively. Together, these results provide experimental evidence indicating that agmatine given systemically and spinally produce marked antinociception at spinal sites in mice. Furthermore, an interaction with glutamate receptors, namely NMDA and trans-ACPD, metabotropic and NMDA-ionotropic origin, by a mechanism similar to that of nitric oxide (NO) inhibitors, seems to account for the agmatine antinociceptive action. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/16765330/Contribution_of_spinal_glutamatergic_receptors_to_the_antinociception_caused_by_agmatine_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(06)00906-1 DB - PRIME DP - Unbound Medicine ER -