• 대한약리학회지
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• 제27권1호
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• pp.53-67
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• 1991

흰쥐 적출 부신에서 DMPP와 McN-A-343의 카테콜아민(CA) 분비작용의 차이와 특성에 대해서 연구한 결과 다음과 같다. DMPP(100 uM)와 McN-A-343(100 uM)은 부신정맥내로 투여시 유의한 카테콜아민 분비작용을 나타내었다. Mol농도로 비교시 McN-A-343의 CA분비작용은 DMPP의 약 1/5정도였다. DMPP나 McN-A-343의 반복투여시 반응 급강현상은 관찰할 수 없었다. DMPP의 CA분비작용은 chlorisondamine이나 desipramine또는 $Ca^{2+}-free$ Krebs + EGTA 관류등의 전처치로 의의있게 억제되었으나, pirenzepine, ouabain 및 physostigmine등 전처치에 의해서는 영향을 받지 않았다. 그러나 atropine 전처치시 DMPP의 분비작용은 오히려 증강되었다. McN-A-343의 CA분비작용은 atropine, pirenzepine, chloriondamine, physostigmine 및 $Ca^{2+}-free$ medium plus EGTA 관류등의 전처치에 의해서현처히 차단되었으나 desipramine등에 의해서는 영향을 받지 않았다. 그러나 ouabain의 전치치시 McN-A-343의 분비효과는 크게 증강되었다. 이상의 실험결과로 보아 DMPP와 McN-A-343은 횐쥐 적출관류 부신에서 현저한 CA분비작용을 일으키며, 이는 $Ca^{2+}$ 의존성 임을 보였으며, DMPP의 분비작용은 부신의 nicotine 수용체의 흥분을 통해서 나타내며, 또한 McN-A-343의 분비작용은 $M_{1}-muscarine$ 수용체의 흥분에 의하여 유발되는 것을 생각된다. DMPP의 분비활성이 McN-A-343보다 훨씬 강력한 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.1-12
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• 1997

As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1$ adenosine heteroreceptor and various evidence suggest that indicate the $A_2$ adenosine receptor is present in the striatum, this study was undertaken to delineate the role of adenosine receptors on the striatal ACh release. Slices from the rat striatum were equilibrated with $[^3H]$choline and then the release amount of the labelled product, $[^3H]$ACh, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, $5\;Vcm^{-1}$, 2 min), was measured, and the influence of various agents on the evoked tritium outflow was investigated. And also, quantitative receptor autoradiography and drug-receptor binding assay were performed in order to confirm the presence and characteristics of $A_1$ and $A_2$ adenosine receptors in the rat striatum. Adenosine $(10{sim}100\;{mu}M)$ and $N^6$-cyclopentyladenosine (CPA, $1{sim}100\;{mu}M)$ decreased the $[^3H]$ACh release in a dose-dependent manner without changing the basal rate of release in the rat striatum. The reducing effects of ACh release by adenosine and CPA were abolished by 8-cyclopentyl-1,3-dipropy-Ixanthine (DPCPX, 2 ${mu}M$), a selective $A_1$, adenosine receptor antagonist, treatment. The effect of adenosine was potentiated markedly by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 ${mu}M$), a specific $A_2$ adenosine receptor antagonist. 2-P-(2-carboxyethyl)phenethylamimo-5'-N- ethylcarboxamidoadenosine hydrochloride (CGS-21680C), in concentrations ranging from 0.01 to 10 ${mu}M$, a recently introduced potent $A_2$ adenosine receptor agonist, increased the $[^3H]$ACh release in a dose related fashion without changing the basal rate of release. These effects were completely abolished by DMPX $(10\;{mu}M)$. In autoradiograrhy experiments, $[^3H]$2-chloro-$N^6$-cyclopentyladenosine ($[^3H]$ CCPA) bindings were highly localized in the hippocampus and the cerebral cortex. Additionally, lower levels of binding were found in the striatum. However, $[^3H]$CGS-21680C bindings were highly localized in the striatal region with the greatest density of binding found in the caudate nucleus and putamen. Lower levels of binding were also found in the nucleus accumbens and olfactory tubercle. In drug-receptor binding assay, binding of $[^3H]$ CCPA to $A_1$ adenosine receptors of rat striatal membranes was inhibited by CPA ($K_i$ = 1.6 nM) and N-ethylcarboxamidoadenosine (NECA, $K_i$ = 12.9 nM), but not by CGS-21680C ($K_i$ = 2609.2 nM) and DMPX ($K_i$ = 19,386 nM). In contrast, $[^3H]$CGS-21680C binding to $A_2$ denosine receptors was inhibited by CGS-21680C ($K_i$ = 47.6 nM) and NECA ($K_i$ = 44.9 nM), but not by CPA ($K_i$ = 2099.2 nM) and DPCPX ($K_i$ = 19,207 nM). The results presented here suggest that both types of $A_1$ and $A_2$ adenosine heteroreceptors exist and play an important role in ACh release in the rat striatal cholinergic neurons.