1998 Fiscal Year Final Research Report Summary
Research on a novel endogenous catecholamine, 6-nitronorepinephrine
| Project/Area Number |
09680771
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Teikyo University |
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Principal Investigator |
NAKAKI Toshio Teikyo University, School of Medicine Department of Pharmacology, Assistant Professor, 医学部, 助教授 (30164148)
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| Project Period (FY) |
1997 – 1998
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| Keywords | nitric oxide / catecholamine / blood vessels / catalase / hydrogen peroxide |
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| Research Abstract |
Vasoactivities of 6-nitronorepineplirine were investigated using rat aorta. 6-Nitronorepinephrine (>100 muM) caused dose-dependent contraction in both endothelium-intact and -denuded aorta, although the latter showed greater contraction than the former. Prazosin (>3 nM), an alpha_1-adrenoceptor antagonist, attenuated significantly the 6- nitronorepinephrine-induced contractions, thereby suggesting the alpha_1-adrenoceptor involvement. Aortic rings prepared from reserpine-pretreated rats showed the 6-nitronorepinephrine-induced a contraction tothe extent similar to those from untreated rats, suggesting that endogenous norepinephrine does not play a role in the 6-nitronorepinephrine-induced contraction. 6-Nitronorepinephrine (>10 muM) potentiated norepinephrine-induced contraction only in the presence of endothelium. The augmentation was attenuated by catalase (1,200U/ml). H_2O_2 (10-300 muM) augmented the norepinephrine-induced contraction only in the endothelium-intact rat aortic rings. 6-Nitronorepinephrine attenuated significantly acetyicholine-induced relaxation. Catalase prevented the 6-nitronorepinephrine-induced inhibition of the acetylcholine-induced relaxation. These results suggest that 6-nitronorepinephrine has a weak txi-adrenoceptor agonistic property and that the endothelium-dependent potentiation by 6-nitronorepinephrine of the norepinephrine-induced contraction is mediated through production of H_20_2. Roles of superoxide in the formation of 6-nitronorepinephrine and distribution of the amine in the brain are being currently investigated.
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