Adenosine induces inositol 1,4,5-trisphosphate receptor-mediated mobilization of intracellular calcium stores in basal forebrain cholinergic neurons.
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-kappaB 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 G(i)-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.
Department of Psychiatry, Harvard Medical School, Veterans Affairs Medical Center, West Roxbury, Massachusetts 02132, USA.
Radhika
R
Basheer
Elda
E
Arrigoni
Hemant S
HS
Thatte
Robert W
RW
Greene
Indu S
IS
Ambudkar
Robert W
RW
McCarley
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D020318:Rats, Long-Evans; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D058906:Purinergic P1 Receptor Agonists; D018160:Receptors, Cytoplasmic and Nuclear; D018047:Receptors, Purinergic P1; D019837:Ryanodine Receptor Calcium Release Channel; C027513:N(6)-cyclohexyladenosine; D000241:Adenosine; D002118:Calcium