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Hiroki Yasuyoshi, Satoshi Kashii, Masashi Kikuchi, Shen Zhang, Yoshihito Honda, Akinori Akaike; New Insight into the Functional Role of Acetylcholine in Developing Embryonic Rat Retinal Neurons. Invest. Ophthalmol. Vis. Sci. 2002;43(2):446-451.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. To examine the effects of acetylcholine (ACh) on glutamate-induced
neurotoxicity in embryonic rat retinal neurons.
methods. Primary cultures were obtained from rat retinas at embryonic days
17 to 19. Cultured cells were exposed to glutamate for 10 minutes,
followed by incubation in glutamate-free medium for 1 hour. Drugs were
added to the incubation medium for 1 to 24 hours until immediately
before glutamate exposure and were removed from culture medium
during glutamate exposure and the postincubation period. The neurotoxic
effects on retinal cultures were quantitatively assessed by the trypan
blue exclusion method.
results. Cell viability was markedly reduced by 10-minute exposure to 500 μM
glutamate followed by a 1-hour incubation in glutamate-free medium.
Incubating the cultures with 1 μM ACh for 12 hours before glutamate
exposure reduced glutamate neurotoxicity. A similar effect was induced
by application of carbachol (1 μM). The protective effect of ACh
against glutamate neurotoxicity was inhibited by a nicotinic
acetylcholine receptor (nAChR) antagonist, mecamylamine (0.5 μM),
whereas a muscarinic acetylcholine receptor (mAChR) antagonist,
atropine (0.5 μM) did not affect ACh-induced protection. In addition,
a similar protection was induced by application of nicotine (1 μM),
but not by muscarine (1 μM). Pretreatment with nicotine induced a
protective effect in a time-dependent manner, ranging from 1 to 12
hours. Pretreatment with nicotine at concentrations ranging from 0.001
to 1 μM induced dose-dependent protection against glutamate
neurotoxicity. Furthermore, the protective action of nicotine was
inhibited by simultaneous application of dopamine D1 receptor
antagonist, SCH23390 (1 μM), with nicotine, whereas a dopamine D2
receptor antagonist, domperidone (1 μM), did not affect
conclusions. These results suggest that pretreatment of cultured rat retinal neurons
with ACh or the nAChR agonists, nicotine and carbachol, has a
protective action against glutamate neurotoxicity through nAChRs and
that the dopamine release induced by nicotinic stimulation subsequently
protects the retinal neurons by way of dopamine D1
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