Interrelationship between dopaminergic receptors and catecholamine secretion from the rat adrenal gland : 흰쥐 부신에서 카테콜아민 분비작용과 도파민 수용체간의 상관성

국문 초록 (Abstract)

도파민 함유세포가 교감신경절에 존재하는 것으로 알려져 있으나, 말초에서 신경전달 물질로써 그의 역할과 작용기전에 대해서 아직까지 알려진 바가 많지 않다. 따라서 본 연구에서는 도파민 D_(2)-수용체의 선택적인 효능약으로 알려진 apomorphine이 흰쥐 적출 관류 부신에서 카테콜아민 (CA) 분비작용에 미치는 영향을 연구코자 시도하여 다음과 같은 연구결과를 얻었다. 10uM Apomorphine의 비교적 낮은 농도를 부신정맥내에 20분간 관류하였을때, 5.32mM ACh, 56mM KC1, 100uM DMPP 및 100uM McN-A-343 등의 투여에 의한 CA 분비작용이 의의 있게 감소되었다. Apomor-phine 농도를 30uM로 증가시켜 관류하였을때 상기약물에 의한 CA 분비작용은 더욱 억제되었으며 또한 BAY-K 8644에 의한 CA 분비 작용도 뚜렷이 억제되었다. 더우기 apomorphine을 100uM의 고농도로 전처치 하였을때, ACh, excess K^(+), DMPP 및 McN-A-343에 의한 CA 분비작용은 현저히 차단되었다.
도파민 D_(2)-수용체 차단제인 metoclopramide (33uM)으로 20분간 관류 하였을때 ACh, DMPP및 McN-A-343에 의한 CA 분비작용은 유의하게 억제된 효과를 나타내었으나 excess K^(+)에 의한 CA 분비작용은 별다른 영향을 받지 않았다. 그러나 metoclopramide (30uM) 존재하에서 30uM apomorphine으로 20분간 전처치 하였을때 excess K^(+) 뿐만아니라 DMPP의 CA 분비작용은 별다른 변화를 받지 않았다.
이상과 같은 실험 연구결과를 종합하여 보면, apomorphine은 cholinergic receptor stimulation 과 membrane depolarization에 의한 CA 분비작용을 용량의존적으로 억제하며, 이러한 작용은 억제성 도파민 수용체를 활성화 시킴으로써 흰쥐 부신 수질의 chromaffin cell 내로 칼슘의 유입을 억제하여 나타나는 것으로 사료된다.

다국어 초록 (Multilingual Abstract)

It has been known for some time that dopamine-containing cells are existed in sympathetic ganglia, i.e., small, intensely fluorescent cells. However, its role and mechanism of action as a peripheral neurotransmitter are poorly understood so far. In the present study, an attempt was made to examine the effect of apomorphine, which is known to be a selective agonist of dopaminergic D_(2)-receptor on secretion of catecholamines(CA) from the isolated perfused rat adrenal gland.
The perfusion of a low concentration of lOuM apomorphine into an adrenal vein for 20 min produced significant reduction in CA secretion induced by 5.32mM ACh, 56mM KC1, 100 uM DMPP and 100 uM McN-A-343. Increasing apomorphine concentration to 30 uM led to more markedly decreased CA secretion as compared to the case of 10uM apomorphine and also did inhibit clearly CA release by 10^(-5)M BAY-K 8644. Furthermore, in adrenal glands preloaded with a higher dose of 100uM apomorphine, CA releases evoked by ACh, excess K^(+), DMPP and McN-A-343 were almost abolished by the drug.
The perfusion of 3.3 X l0^(-5)M metoclopramide, which is well-known as a selective dopaminergic D_(2) antagonist, produced significantly inhibitory effect of CA release by ACh, DMPP and McN-A-343 but did not affect that by excess K^(+). However, preloading of 30 uM apomorphine in the presence of metoclopramide did not modify the CA secretory effect of excess K^(+) and DMPP.
These experimental results demonstrate that apomorphine causes dose-dependent inhibition of CA secretion by cholinergic receptor stimulation and also by membrane depolarization from the isolated perfused rat adrenal gland, suggesting that these effects appear to be exerted by inhibiting influx of extracellular calcium into the rat adrenal medullary chromaffin cells through activation of inhibitory dopaminergic receptors.

목차 (Table of Contents)

• CONTENTS
• 국문초록 = 1
• Ⅰ. INTRODUCTION = 3
• Ⅱ. MATERIALS AND METHODS = 6
• Experimental Animals = 6
• Perfusion of Adrenal Gland = 8
• Drug Adrninistration = 8
• Collection of Perfusate = 8
• Measurement of Catecholamines = 9
• Drugs and Their Sources = 10
• Ⅲ. RESULTS = 11
• Effect of 10uM apomorphine on CA secretion evoked by ACh, excess K^(+), DMPP and McN-343 from perfused rat adrenal glands = 11
• Effect of 30uM-apomorphine on CA secretion evoked by ACh, excess K^(+), DMPP, McN-A-343 and BAY-K 8644 from the perfused rat adrenal glands = 15
• Effect of 100uM apomorphine on CA secretion evoked by ACh, excess K^(+), DMPP and McN-A 343 from the perfused rat adrenal glands = 21
• Effect of metoclopramide on CA secretion evoked by ACh, excess K^(+), DMPP and McN-A-343 from the perfused rat adrenal glands = 25
• Effect of metoclopramide on inhibition by apomorphine of CA secretory reponses stimulated by excess K^(+) and DMPP = 29
• Ⅳ. DISCUSSION = 32
• Ⅴ. SUMMARY = 39
• REFERENCES = 41