| Project/Area Number |
05454661
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Nerve anatomy/Neuropathology
|
|---|
| Research Institution | Osaka University (1994-1995)
Osaka City University (1993) |
|---|
Principal Investigator |
FURUYAMA Shinobu Osaka University, School of Medicine, professor, 医学部, 教授 (90151571)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FURUYAMA Tatsuo Osaka University, School of Medicine, instructor, 医学部, 助手 (20238702)
高木 宏 大阪市立大学, 医学部, 教授 (30163174)
|
|---|
| Project Period (FY) |
1993 – 1995
|
| Project Status |
Completed (Fiscal Year 1995)
|
| Budget Amount *help |
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥5,800,000 (Direct Cost: ¥5,800,000)
|
|---|
| Keywords | soluble guanylate cyclase / mitric oxide / cGMP-dependent kinase / isozymes / subunits / brain / in situ hvbridization / mRNA / cGMP-dependent protein kinase / α2サブユニット / cyclicGMP‐dependent protein kinase / 一酸化窒素 / NO synathase / 脳 |
|---|
| Research Abstract |
Nitric oxide (NO) is an important intercellular messenger in the vessels and nervous system. NO activate guanylate cyclase to produce cGMP.Endothelial cells contain both NO and soluble guanylate cyclase (sGC) which exists as a heterodimer, while it is uncertain whether neurons contain both NO and soluble guanylate cyclase. First, using in situ hybridization we identified the localization of mRNA for alpha1 and beta1 subunits of sGC in the brain. Both alpha1 and beta1 subunits was expressed widely but unevenly in the brain. Strong expressions for both subunits were detected in many regions such as the neostriatum, accumbens nucleus, olfactory tubercle, and locus coeruleus These regions are suggested to contain active sGC as a target for NO.On the other hand, several regions did express no or only weak signals for alpha1 but expressed strong signals for beta1 subunits, suggested the presence of other alpha subunits in therse regions. Second, since little is known about receptor proteins
… More
for cGMP in the nervous system. cGMP-dependent protein kinase (GK) is one of main intracellular receptors for cGMP.Two types of GKs exists in vertebrate cells, a type 1 and type 2 form. The type 1 GK (GK1) exists as a homodimer and is generally extracted from soluble fraction of various tissues, while the type 2 GK (GK2) is a membrane-bound monomer. GK1 is widely distributed and predominant form in many tissues of vertebrate. Despite the abundant expression of GK1 in smooth muscle and many periphery tissues, in the brain its presence has been reported only in the Purkinje cells of the cerebellum by using immunohistochemistry. In the present sudy we displayd distinct distribution of GK1 and GD2, and more extensive distribution for GK1and GK2. Strong expressions of GK1 in the hippocampus and cerebellum suggest a role for this kinase in mediating the long-term potentiation and long-term depression of NO via activation of sGC in these regions. On the other hand, strong expressions of GK2 in the thalamus support a role for the kinase in mediating another actions of NO there. The wide distributions of GK1 and GK2 in the brain suggests that cGMP-mediated protein phosphorylation occurs in many brain regions. Less
|
