| Project/Area Number |
61480119
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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 pharmacology
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| Research Institution | Yokohama City University |
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Principal Investigator |
MISY Yoshimi Yokohama City University . Professor, 医学部, 教授 (10025687)
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| Co-Investigator(Kenkyū-buntansha) |
GOSHIMA Yoshio Yokohama City University . Research Addociate, 医学部, 助手 (00153750)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | DOPA release / Regulatory actions on dopamine and norepinephrine release / Neuroactive substance / Presynaptic facilitatory <beta>-adrenoceptors / Presynaptic inhibitory dopamine receptors / 線条体 / ドパミン・ノルエピネフリン遊離制御作用 / 視床下部 / ドーパ / 神経伝達物質 / 【Ca^(2+)】依存性 / TTX感受性 / チロシン水酸化酵素 / シナプス前β-アドレナリン受容体 / シナプス前ドパミン受容体 |
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| Research Abstract |
DOPA, a precursor of dopamine (DA), has been generally accepted to act through its conversion to DA by DOPA-decarboxylase. However, depolarization released endogenous DOPA from superfused slices of rat striata. We compared the characteristics of the DOPA release with those of DA and also studied actions of exogenously applied DOPA on the release of DA and norepinephrine (NE).
1. Electrical field stimulation with biphasic impulses (2 Hz) released DOPA and DA via a terodo toxin-sensitive and Ca^<2+>-dependent process. High K^+ 715 mM) also released DOPA and DA via a Ca^<2+> dependent process. In slices superfused with ^3H-tyrosine (1 <micro>M)-containing medium, high K^+ (15 and 60 mM) released DOPA and DA with a concentration-dependent decrease in tyrosine hydroxylase activity, ^3H-H_2O formation, followed by a concentration-dependent increase after the release of DA ended. DOPA appears to be released by an excitation-secretion coupling process.
2. In striatal alices, DOPA 30 nM facilitated the evoked release of DA without increases in the sponyaneous release and tissue content of DA. In the presence of NSD-1055, a DOPA-decarboxylase inhi bitor, DOPA 10 nM to 1 <micro>M produces biphasic actions on the evoked release of DA, facilitation at 30 nM via presynaptic <beta>-adrenoceptors and inhibition at 1 <micrn>M via presynaptic DA receptor Similar biphasic actions of DOPA on the release of DA and NE were also seen in rat hypothalamic slices.
A transmitter-like release of DOPA was seen in rat striatal slices. Biphasic regulatory actions of DOPA itself on the release of DA and NE seen in rat striatal and hypothalamic slices. These findings support a working hypothesis that DOPA plays a role as a neuroactive substance in these brain regions.
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