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Catecholamine 및 그 합성효소 활성에 미치는 clonidine작용에 대한 tranylcypromine의 영향

Catecholamine 및 그 합성효소 활성에 미치는 clonidine작용에 대한 tranylcypromine의 영향
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(The) Influence of Tranylcypromine on Catecholamine & Catecholamine Synthesizing Enzymes Changed by Clonidine
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대학원 약학과
이화여자대학교 대학원
α_(2)-adrenergic agonist 인 clonidine 과 Monoamineoxidase Inhibitor계 항우울약이, 혈압변화와 밀접한 관계가 있는 신경전달 물질의 합성, 유리 및 재흡수에 크게 영향을 미친다는 보고가 있어, 중추성 항고혈압약인 clonidine에 의한 뇌와 부신 중의 catecholamine 함량 및 그 합성효소 활성의 변화와 이에 대한 tranylcypromine(TCP)의 영향을 알아보고자, 흰쥐에게 clonidine과 tranylcypromine을 단독 또는 tranylcypromine 전처리 후 clonidine을 5일간 주사하고 적출한 선조체, 시상하부, 뇌간 및 부신에 있어서의 norepinephrine 함량을 fluorometric method로 tyrosine hydroxylase (TH)와 phenylethanolamine-N-methyl transferase (PNMT) 활성을 radiometric method로 측정하여 다음과 같은 결과를 얻었다. 1. Clonidine은 시상하부에서 norepinephrine양을 증가시켰고, 뇌간에서 tyrosine hydroxylase 활성을 감소시켰다. 2. Tranylcypromine은 뇌간에서 norepinephrine 양을 증가시켰고, 선조체, 시상하부 및 뇌간에서 tyrosine hydroxylase 활성을 증가시켰다. 3. Clonidine에 의한 뇌간에 있어서의 tyrosine hydroxylase 활성 감소효과는 tranylcypromine 전처리로 제거되었다. 4. Clonidine 과 tranylcypromine 둘다 부신 중의 catecholamine양 및 phenylethanolamine - N - methyltransferase 활성에는 영향을 미치지 않았다.;It has been reported that α_(2)-adrenergic agonist, clonidine and MAOI, tranylcypromine would influence on synthesis, release and reuptake of neurotransmitter correlated to blood pressuer change. In the present work the effects of tranylcypromine on changes in catecholamine content & catecholamine synthesizing enzyme activities following clonidine administration in adrenal glands and brain regions of rats were investigated. Four groups of 5 rats were intraperitoneally injected with saline, clonidine, tranylcypromine alone, and clonidine after pretreatment with tranylcypromine, twice daily for 5 days. After killed by decapitation, hypothalamus, brain stem, striatum, and adrenal gland of rat were dissected to measure the norepinephrine content by fluorometric method and tyrosine hydroxylase (TH) & phenylethanolamine-N-methyltransferase (PNMT) activities by radiometric method. The summarized results are as follows: 1) Administration of clonidine alone (100㎍/㎏, i.p, twice daily for 5 days) increased norepinephrine content in hypothalamus, and decreased tyrosine hydroxylase activity in brain stem. 2) Administration of tranylcypromine alone (10㎎/㎏, i.p, twice daily for 5 days) increased norepinephrine content in brain stem, and enhanced tyrosine hydroxylase activity in striatum, hypothalamus, and brain stem. 3) Inhibition of tyrosine hydroxyalse activity in brain stem by clonidine was prevented by pretreatment with tranylcy-promine. 4) Epinephrine & norepinephrine content and phenylethanolamine-N-methyltransferase activity were not significantly altered in adrenal gland by clonidine or tranylcypromine.
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