2004 Fiscal Year Final Research Report Summary
Vesicular Acetylcholine Release from Astrocytes by Adenosine Signal
| Project/Area Number |
15590199
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General physiology
|
|---|
| Research Institution | Hyogo College of Medicine |
|---|
Principal Investigator |
YAJIMA Yukio Hyogo College of Med., Faculty of Med., Associate Professor, 医学部, 助教授 (10068489)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHIZAKI Tomoyuki Hyogo College of Med., Faculty of Med., Professor, 医学部, 教授 (00221474)
YAMAMOTO Satoshi Hyogo College of Med., Faculty of Med., Associate Professor, 医学部, 助教授 (60220464)
NAGATA Tetsu Hyogo College of Med., Faculty of Med., Assistant Professor, 医学部, 講師 (60131588)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Astrocyte / Striatum / Acetylcholine / Vesicular transport / Adenosine / Adenosine A_<2a> receptor / PKA |
|---|
| Research Abstract |
Cultured rat striatal astrocytes expressed choline acetyltransferase. Adenosine or CGS21680, an agonist of A_<2a> adenosine receptors, stimulated acetylcholine(ACh) release and the effect was inhibited by DMPX, an antagonist of A_<2a> adenosine receptors, H-89, an inhibitor of protein kinase A(PKA), or brefeldin A, a vesicular transport inhibitor. Synaptic vesicle fractions, that are separated with a sucrose-density gradient centrifugation, contains high concentrations of ACh. Adenosine or CGS21680 increase intracellular Ca^<2+> concentrations in astrocytes, and the increase was inhibited by DMPX,H-89, or brefeldin A, but not by neomycin and U73122, an inhibitor of phospholipase C, xestospongin, an inhibitor of IP_3 receptors, ryanodine, an inhibitor of ryanodine receptors, octanol, an inhibitor of gap-junction, or cadmium, an inhibitor of voltage-sensitive Ca^<2+> channels. The results of the present study indicate that adenosine stimulates vesicular release of ACh from astrocytes in a Ca^<2+> -dependent manner via an A_<2a> adenosine receptor/PKA signaling pathway. This may provide a new strategy targeting astrocytes in the development of anti-dementia drugs.
|
