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Effect of agmatine on DAMGO-induced mu-opioid receptor down-regulation and internalization via activation of IRAS, a candidate for imidazoline I(1) receptor.

Abstract：

:Agmatine, an endogenous ligand for imidazoline I(1) receptor, has previously been shown to prevent opioid tolerance in rats and mice, but the cellular mechanisms remain unknown. In the present study, the effects of agmatine activation on imidazoline I(1) receptor on the desensitization, down-regulation and internalization of micro opioid receptor were investigated. Two cell lines, CHO cells transfected micro opioid receptor (CHO-micro cells) and co-transfected micro opioid receptor and imidazoline I(1) receptor antisera-selected protein (IRAS) (CHO-micro/IRAS cells), were used. In both CHO-micro cells and CHO-micro/IRAS cells, agmatine (0.01-10 microM) did not affect the desensitization of micro opioid receptor induced by [d-Ala(2), N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) (10 microM) treatment for 30 min. However, agmatine (0.1-100 nM) co-pretreatment with DAMGO (1 microM) for 12 h concentration-dependently inhibited DAMGO-induced down-regulation of micro opioid receptor in CHO-micro/IRAS cells, but not in CHO-micro cells. Efaroxan, the I(1)/alpha(2)-adrenoceptors mix antagonist, completely reversed the inhibitory effect of agmatine, suggesting the participation of imidazoline I(1) receptor. In addition, agmatine (1-100 nM) inhibited DAMGO-induced internalization of micro opioid receptor in CHO-micro/IRAS cells, which was reversed by efaroxan as well. While treatment with DAMGO (1 microM) or co-treatment with agmatine (1-100 nM) for 12 h failed to affect the mRNA level of micro opioid receptor. Taken together, these results indicate that the inhibitory effect of agmatine on tolerance in vitro might be related to attenuation of the internalization and down-regulation of micro opioid receptor via activation of imidazoline I(1) receptor.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Gao Y,Li F,Wu N,Su RB,Liu Y,Lu XQ,Liu Y,Li J

doi

10.1016/j.ejphar.2008.09.020

subject

Has Abstract

pub_date

2008-12-03 00:00:00

pages

18-23

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(08)00962-X

journal_volume

599

pub_type

杂志文章

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Effect of agmatine on DAMGO-induced mu-opioid receptor down-regulation and internalization via activation of IRAS, a candidate for imidazoline I(1) receptor.