| Project/Area Number |
13670855
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | University of Occupational and Environmental Health |
|---|
Principal Investigator |
YANAGIHARA Nobuyuki UOEH, School of Medicine, Professor, 医学部, 教授 (80140896)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TOYOHIRA Yumiko UOEH, School of Medicine, Instructor, 医学部, 助手 (90269051)
ASAYAMA Kohtaro UOEH, School of Medicine, Associate Professor, 医学部, 助教授 (70129310)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Keywords | Adrenal medulla / Catecholamine / Obese children / Orexin-A / Orexin receptor 1 / Protein kinase C / Synthesis / Tyrosine hydroxylase / オレキシン受容体 / 副腎髄質細胞 / RT-PCR / オレキシンA / 遊離 / ヒト血中オレキシンA濃度 |
|---|
| Research Abstract |
Orexin-A and orexin-B, also known as hypocretin-1 and hypocretin-2, have recently been identified as hypothalamic peptides derived from a precursor, prepro-orexin, in neurons located within and around the lateral and posterior hypothalamus in the rat brain. To determine the role of orexin-A in peripheral metabolic processes, we examined direct effects of orexin-A on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells. 1) Incubation of cells with orexin-A (100 pM) for 20 min caused a small but significant increase in ^<14>C-catecholamine synthesis from [^<14>C] tyrosine, but not from L-3,4-dihydroxyphenyl [3-^<14>C] alanine. Orexin-A (100 pM) potentiated the stimulatory effects of acetylcholine (0.3 mM) ^<14>C-catecholamine synthesis. 2) Orexin-A significantly increased tyrosine hydroxylase activity, which was evident at 1 pM and maximal at 100 pM. 4β-Phorbol-12β-myristate-13α-acetate, an activator of protein kinase C, did not enhance the stimulatory effects of orexin-A on tyrosine hydroxylase activity, while H-7 and staurosporine, inhibitors of protein kinase C, nullified the effects of orexin-A. 3) Orexin-A had little effect on catecholamine secretion from the cells. 4) Orexin receptor 1 (OX_1R) but not orexin receptor 2 (OX_2R) mRNA was detected in bovine adrenal medullary cells by reverse transcriptase-polymerase chain reaction.
These findings suggest that orexin-A activates tyrosine hydroxylase and then stimulates catecholamine synthesis, probably via activation of the OX_1R-protein kinase C pathway in adrenal medullary cells. This information helps to understand the biochemical basis of the effect of orexins on metabolic homeostasis in the obesity of adults as well as children.
|
