| Project/Area Number |
62480124
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
FUJISAWA Hitoshi Asahikawa Medical College ・ Professor, 医学部, 教授 (10027039)
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| Co-Investigator(Kenkyū-buntansha) |
KAMESHITA Isamu Asahikawa Medical College ・ Associate Professor, 医学部, 助教授 (60127941)
YAMAUCHI Takashi Asahikawa Medical College ・ Associate Professor, 医学部, 助教授 (90041813)
TOBIMATSU Takamasa Asahikawa Medical College ・ Instructor, 医学部, 助手 (30188768)
KITANI Takako Asahikawa Medical College ・ Research Associate, 医学部, 教務職員 (70101417)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | Tyrosine Hydroxylase / Tryptophan Hydroxylase / Catecholamine / Phospholipid / Calmodulin Dependent Protein Kinase II / Autophosphorylation / cDNAクローニング / セロトニン / カルモデュリン依存性蛋白質リン酸化酵素II / 自己リン酸化反応 |
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| Research Abstract |
Tyrosine hydroxylase which catalyzes the rate-limiting step in the biosynthetic pathway of catecholamines in the nervous system was found to be converted to inactive/stable form by catecholamines, end-products of tyrosine hydroxylase. Among a variety of catechols or related compounds tested for their ability to convert the enzyme to inactive/stable form, only catechols possessing amino group on the side chain and no negatively charged side chain were effective at a concentration as low as 10^<-7> M. The inactive form of the enzyme was dramatically activated by the action of cyclic AMP-dependent protein kinase. The human enzyme as well as the rat enzyme appeared to be regulated by similar mechanism.
Tryptophan hydroxylase which catalyzes the rate-limiting step in the biosynthesis of serotonin in the central nervous system was markedly activated by the addition of phosphatidylinositol or phosphatidylserine and the enzyme once activated was gradually inactivated by subsequent incubation with the phospholipids. The inactivation was found to be blocked by the addition of ferrous ion and dithiothreitol. Gel filtration analysis revealed that the enzyme activated by the phospholipids was bound to the phospholipids and that the enzyme inactivated by the subsequent incubation was not bound to the phospholipids. the results suggest The possible involvement of cellular membranes in the regulation of this enzyme.
Calmodulin-dependent protein kinase II has been demonstrated to be involved in the regulation of both tyrosine hydroxylase and tryptophan hydroxylase in the central nervous system. cDNA clones for three distinct types of rat brain calmodulin-dependent protein kinase II were isolated and a cDNA sequence for the coding region was determined. The predicted amino acid sequence of this kinase revealed the domain structure of the kinase.
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