کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1910790 1046787 2008 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A glutathione deficit alters dopamine modulation of L-type calcium channels via D2 and ryanodine receptors in neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
A glutathione deficit alters dopamine modulation of L-type calcium channels via D2 and ryanodine receptors in neurons
چکیده انگلیسی

Synthesis of glutathione, a major redox regulator, is compromised in schizophrenia. We postulated that the resulting glutathione deficit via its effect on redox-sensitive proteins could contribute to dysfunction of some neurotransmitter systems in schizophrenia. We investigated whether a glutathione deficit, induced by a blocker of glutathione synthesis, L-buthionine-(S,R)-sulfoximine, affects intracellular pathways implicated in dopamine signaling in neurons, namely dopamine modulation of calcium responses to NMDA. Such a glutathione deficit changed the modulation of responses by dopamine, from enhanced responses in control neurons (likely via D1-type receptors) to decreased responses in low-glutathione neurons (via D2-type receptors). This difference in dopamine modulation was due to a different modulation of L-type calcium channels activated during NMDA stimulation: dopamine enhanced function of these channels in control neurons but decreased it in low-glutathione neurons. The effect of a glutathione deficit on dopamine signaling was dependent on the redox-sensitive ryanodine receptors (RyRs), whose function was enhanced in low-glutathione neurons. This suggests that enhanced RyRs in low-glutathione neurons strengthens intracellular calcium-dependent pathways following activation of D2-type receptors and causes a decrease in function of L-type channels. This represents a mechanism by which dopaminergic systems could be dysfunctional under conditions of impaired glutathione synthesis as in schizophrenia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 44, Issue 6, 15 March 2008, Pages 1042–1054
نویسندگان
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