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The Journal of Neuroscience, September 1, 2002, 22(17):7680-7686
Adenosine Induces Inositol 1,4,5-Trisphosphate Receptor-Mediated
Mobilization of Intracellular Calcium Stores in Basal Forebrain
Cholinergic Neurons
Radhika
Basheer1,
Elda
Arrigoni2,
Hemant S.
Thatte3,
Robert W.
Greene4,
Indu S.
Ambudkar5, and
Robert W.
McCarley1
Departments of 1 Psychiatry, 2 Neurology,
and 3 Surgery, Harvard Medical School, Veterans Affairs
Medical Center, West Roxbury, Massachusetts 02132, 4 Department of Psychiatry, University of Texas
Southwestern Medical Center and Dallas Veterans Affairs Medical Center,
Dallas, Texas 75390, and 5 Secretory Physiology
Section, Gene Therapy and Therapeutics Branch, National Institute of
Dental and Craniofacial Research, National Institutes of Health,
Bethesda, Maryland 20892
In the cholinergic basal forebrain, we found previously that the
extracellular adenosine concentration increase that accompanies sleep
deprivation, acting via the A1 receptor, led to activation of the transcription factor nuclear factor- B and to the upregulation of A1 adenosine receptor mRNA. We thus began to examine
intracellular signaling mechanisms. We report here that adenosine,
acting in a dose-dependent manner and predominantly via A1
receptors, stimulated IP3 receptor-regulated calcium
release from intracellular stores. To the best of our knowledge, this
calcium signaling pathway effect is a novel action of the
Gi-coupled A1 adenosine receptor in neurons. Moreover, this calcium mobilization was not seen at all in
noncholinergic neurons but was present in a large proportion of
cholinergic neurons. These data suggest a potential role for a
calcium-signaling pathway in adenosine-induced long-term effects of
sleep deprivation and a key role for cholinergic neurons in this process.
Key words:
adenosine; cholinergic basal forebrain; A1
adenosine receptor; intracellular calcium mobilization; inositol
1,4,5-trisphosphate receptor activation; sleep deprivation
Copyright © 2002 Society for Neuroscience 0270-6474/02/22177680-07$05.00/0
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