Search

Your search keyword '"Hieda E"' showing total 2 results
Start Over Author "Hieda E"
2 results on '"Hieda E"'

1. Muscarinic receptors acting at pre- and post-synaptic sites differentially regulate dopamine/DARPP-32 signaling in striatonigral and striatopallidal neurons.

Author

Kuroiwa M, Hamada M, Hieda E, Shuto T, Sotogaku N, Flajolet M, Snyder GL, Hendrick JP, Fienberg A, and Nishi A

Subjects
Animals, Benzazepines pharmacology, Corpus Striatum drug effects, Dopamine Antagonists pharmacology, Male, Mice, Mice, Inbred C57BL, Neurons drug effects, Oxotremorine pharmacology, Phosphorylation drug effects, Receptors, Dopamine D1 antagonists & inhibitors, Signal Transduction drug effects, Substantia Nigra drug effects, Synapses drug effects, Synapses metabolism, Corpus Striatum metabolism, Dopamine metabolism, Dopamine and cAMP-Regulated Phosphoprotein 32 metabolism, Neurons metabolism, Receptors, Muscarinic metabolism, Signal Transduction physiology, Substantia Nigra metabolism
Abstract

Muscarinic receptors, activated by acetylcholine, play critical roles in the functional regulation of medium spiny neurons in the striatum. However, the muscarinic receptor signaling pathways are not fully elucidated due to their complexity. In this study, we investigated the function of muscarinic receptors in the striatum by monitoring DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa) phosphorylation at Thr34 (the PKA-site) using mouse striatal slices. Treatment of slices with a non-selective muscarinic receptor agonist, oxotremorine (10 μM), rapidly and transiently increased DARPP-32 phosphorylation. The increase in DARPP-32 phosphorylation was completely abolished either by a dopamine D(1) receptor antagonist (SCH23390), tetrodotoxin, genetic deletion of M5 receptors, muscarinic toxins for M1 and M4 receptors, or 6-hydroxydopamine lesioning of dopaminergic neurons, whereas it was enhanced by nicotine. Analysis in D(1)-DARPP-32-Flag/D(2)-DARPP-32-Myc transgenic mice revealed that oxotremorine increases DARPP-32 phosphorylation selectively in D(1)-type/striatonigral, but not in D(2)-type/striatopallidal, neurons. When D(1) and D(2) receptors were blocked by selective antagonists to exclude the effects of released dopamine, oxotremorine increased DARPP-32 Thr34 phosphorylation only in D(2)-type/striatopallidal neurons. This increase required activation of M1 receptors and was dependent upon adenosine A(2A) receptor activity. The results demonstrate that muscarinic receptors, especially M5 receptors, act at presynaptic dopaminergic terminals, regulate the release of dopamine in cooperation with nicotinic receptors, and activate D(1) receptor/DARPP-32 signaling in the striatonigral neurons. Muscarinic M1 receptors expressed in striatopallidal neurons interact with adenosine A(2A) receptors and activate DARPP-32 signaling., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Published
2012
Full Text
View/download PDF

2. Role of adrenoceptors in the regulation of dopamine/DARPP-32 signaling in neostriatal neurons.

Author

Hara M, Fukui R, Hieda E, Kuroiwa M, Bateup HS, Kano T, Greengard P, and Nishi A

Subjects
Adrenergic alpha-2 Receptor Antagonists, Animals, Catalytic Domain drug effects, Catalytic Domain physiology, Cyclic AMP Response Element-Binding Protein metabolism, Dopamine and cAMP-Regulated Phosphoprotein 32 drug effects, GTP-Binding Protein alpha Subunits, Gi-Go drug effects, GTP-Binding Protein alpha Subunits, Gi-Go metabolism, Male, Mice, Mice, Inbred C57BL, Neostriatum drug effects, Neurons drug effects, Organ Culture Techniques, Parkinson Disease drug therapy, Parkinson Disease metabolism, Parkinson Disease physiopathology, Phosphorylation drug effects, Receptor, Adenosine A2A drug effects, Receptor, Adenosine A2A metabolism, Receptors, Adrenergic drug effects, Receptors, Adrenergic, alpha-2 metabolism, Receptors, Adrenergic, beta-1 drug effects, Receptors, Adrenergic, beta-1 metabolism, Receptors, Dopamine D2 drug effects, Receptors, Dopamine D2 metabolism, Signal Transduction drug effects, Signal Transduction physiology, Threonine metabolism, Dopamine metabolism, Dopamine and cAMP-Regulated Phosphoprotein 32 metabolism, Neostriatum metabolism, Neurons metabolism, Receptors, Adrenergic metabolism
Abstract

Studies in animal models of Parkinson's disease have revealed that degeneration of noradrenaline neurons is involved in the motor deficits. Several types of adrenoceptors are highly expressed in neostriatal neurons. However, the selective actions of these receptors on striatal signaling pathways have not been characterized. In this study, we investigated the role of adrenoceptors in the regulation of dopamine/dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa (DARPP-32) signaling by analyzing DARPP-32 phosphorylation at Thr34 [protein kinase A (PKA)-site] in mouse neostriatal slices. Activation of beta(1)-adrenoceptors induced a rapid and transient increase in DARPP-32 phosphorylation. Activation of alpha(2)-adrenoceptors also induced a rapid and transient increase in DARPP-32 phosphorylation, which subsequently decreased below basal levels. In addition, activation of alpha(2)-adrenoceptors attenuated, and blockade of alpha(2)-adrenoceptors enhanced dopamine D(1) and adenosine A(2A) receptor/DARPP-32 signaling. Chemical lesioning of noradrenergic neurons mimicked the effects of alpha(2)-adrenoceptor blockade. Under conditions of alpha(2)-adrenoceptor blockade, the dopamine D(2) receptor-induced decrease in DARPP-32 phosphorylation was attenuated. Our data demonstrate that beta(1)- and alpha(2)-adrenoceptors regulate DARPP-32 phosphorylation in neostriatal neurons. G(i) activation by alpha(2)-adrenoceptors antagonizes G(s)/PKA signaling mediated by D(1) and A(2A) receptors in striatonigral and striatopallidal neurons, respectively, and thereby enhances D(2) receptor/G(i) signaling in striatopallidal neurons. alpha(2)-Adrenoceptors may therefore be a therapeutic target for the treatment of Parkinson's disease.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results