Activation of the TRPV1 channel attenuates N-methyl-D-aspartic acid-induced neuronal injury in the rat retina

被引：29

作者：

Sakamoto, Kenji ^{[1
]}

Kuroki, Taiyo ^{[1
]}

Okuno, Yui ^{[1
]}

Sekiya, Haruna ^{[1
]}

Watanabe, Akihiro ^{[1
]}

Sagawa, Tomonori ^{[1
]}

Ito, Hiroko ^{[1
]}

Mizuta, Aya ^{[1
]}

Mori, Asami ^{[1
]}

Nakahara, Tsutomu ^{[1
]}

Ishii, Kunio ^{[1
]}

机构：

[1] Kitasato Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol, Minato Ku, Tokyo 1088641, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2014年 / 733卷

关键词：

Retina; N-methyl-D-aspartic acid; Transient receptor potential vanilloicl typel; Capsaicin; GENE-RELATED PEPTIDE; ISOLATED-PERFUSED HEART; INDUCED RENAL INJURY; VANILLOID; AGONIST; SUBSTANCE-P; GUINEA-PIG; CELL-DEATH; HISTOLOGICAL PROTECTION; ISCHEMIA-REPERFUSION; INDUCED APOPTOSIS;

D O I：

10.1016/j.ejphar.2014.03.035

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Capsaicin, a transient receptor potential vanilloid type1 (TRPV1) agonist, has been reported to protect against ischemia-reperfusion injury in various organs, including the brain, heart, and kidney, whereas activation of TRPV1 was also reported to contribute to neurodegeneration, including pressure-induced retinal ganglion cell death in vitro. We histologically investigated the effects of capsaicin and SA13353, TRPV1 agonists, on retinal injuiy induced by intravitreal N-methyl-D-aspartic acid (NMDA; 200 nmol/eye) in rats in vivo. Under ketamine/xylazine anesthesia, male Sprague-Dawley rats were subjected to intravitreal NMDA injection. Capsaicin (5.0 nmol/eye) was intravitreally admianeously with NMDA injection. SA13353 (10 mg/kg) was intraperitoneally administered 15 min before NMDA injection. Morphometric evaluation at 7 days after NMDA injection showed that intravitreal NMDA injection resulted in ganglion cell loss. Capsaicin and SA13353 almost completely prevented this damage. Treatment with capsazepine (TRPV1 antagonist, 0.5 nmol/eye), CGRP (8-37) (calcitonin gene related peptide (CGRP) receptor antagonist, 0.5 pmol/eye), or RP67580 (Lachykinin NK1 receptor antagonist, 0.5 nmol/eye) almost completely negated the protective effect of capsaicin in the NMDA-injecLed rats. Seven clays after intravitreal NMDA injection, the cell number of retinal ganglion cell was significantly smaller than in the eye that had received capsaicin in B6.Cg-TgN(Thy1-CFP)23Jrs/J transgenic mice that express the enhanced cyan fluorescent protein in retinal ganglion cells in the retina. These results suggested that activation of TRPV1 protects retinal neurons from the injury induced by intravitreal NMDA in rats in vivo. Activation of CGRP and Lachykinin NK1 receptors is possibly involved in underlying protective mechanisms. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：13 / 22

页数：10

共 51 条

[1] Inhibition of NMDA receptors and nitric oxide synthase reduces ischemic injury of the retina [J].