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Hiroki Yasuyoshi, Satoshi Kashii, Shen Zhang, Akihiro Nishida, Tomofusa Yamauchi, Yoshihito Honda, Yukiyasu Asano, Sachi Sato, Akinori Akaike; Protective Effect of Bradykinin against Glutamate Neurotoxicity in Cultured Rat Retinal Neurons. Invest. Ophthalmol. Vis. Sci. 2000;41(8):2273-2278.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. To identify the localization and expression of bradykinin (BK)-B2
receptors in rat retina and examine the effects of BK on
glutamate-induced neurotoxicity using cultured rat retinal neurons.
methods. An immunohistochemical study using a specific antibody against BK-B2
receptor was performed with rat retina. Primary cultures were obtained
from the retina of fetal rats (gestation day 17–19). Expression of
BK-B2 receptor mRNA was determined by reverse transcription–polymerase
chain reaction (RT-PCR) using total RNA obtained from cultured retinal
neurons. Cultured cells were exposed to glutamate (1 mM) for 10 minutes
and followed by incubation in glutamate-free medium for 1 hour. The
effects of BK were assessed by simultaneous application of BK with
glutamate. The neurotoxic effects on retinal cultures were
quantitatively assessed by the trypan blue exclusion method.
results. Immunohistochemical study demonstrated that BK-B2 receptors were
expressed in the ganglion cell, inner nuclear layers, and outer nuclear
layers. Furthermore, BK-B2 receptor mRNA expression was observed in
cultured retinal neurons. Cell viability was markedly reduced by
10-minute exposure to 1 mM glutamate followed by a 1-hour incubation in
glutamate-free medium. Simultaneous application of BK at concentrations
of 0.001 to 1 μM with glutamate demonstrated dose-dependent
protection against glutamate neurotoxicity. The protective action of BK
(1 μM) was inhibited by simultaneous application of BK-B2 receptor
antagonist, Hoe140 (1 μM). Furthermore, 1 μM BK had protective
effects on neurotoxicity induced by 1 μM ionomycin, a calcium
ionophore, and sodium nitroprusside (SNP, 500 μM), a nitric oxide
(NO)–generating agent. However, BK did not inhibit neurotoxicity
induced by 3-morpholinosydnonimine (SIN-1, 10 μM), an NO and oxygen
conclusions. These results suggest that BK-B2 receptors were distributed in rat
retinas and cultured retinal neurons and that BK had a protective
action against glutamate neurotoxicity through BK-B2 receptors in
cultured retinal neurons. It is suggested that BK-induced protection
against glutamate neurotoxicity took place downstream to NO generation
and upstream to oxygen radical generation.
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