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D-Amphetamine Causes Dual Actions on Catecholamine Release from the Rat Adrenal Medulla
임건한,나광문,민선영,서유석,박찬원,임동윤 대한약리학회 2005 The Korean Journal of Physiology & Pharmacology Vol.9 No.1
The present study was designed to examine the effect of d-amphetamine on CA release from the isolated perfused model of the rat adrenal gland, and to establish its mechanism of action. D- amphetamine (10~100μM), when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced the CA secretory responses evoked by ACh (5.32×10-3 M), excess K+ (5.6×10-2 M, a membrane depolarizer), DMPP (10-4 M, a selective neuronal nicotinic Nn-receptor agonist) and McN-A-343 (10-4 M, a selective M1-muscarinic agonist) only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, d-amphetamine (30μM) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type Ca2+ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic Ca2+ ATPase only for the first period (4 min). However, in the presence of high concentration (500μM), d-amphetamine rather inhibited the CA secretory responses evoked by the above all of secretagogues. Collectively, these experimental results suggest that d-amphetamine at low concentrations enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization, but at high concentration it rather inhibits them. It seems that d-amphetamine has dual effects as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that these actions of d-amphetamine are probably relevant to the Ca2+ mobilization through the dihydropyridine L-type Ca2+ channels located on the rat adrenomedullary chromaffin cell membrane and the release of Ca2+ from the cytoplasmic store
D-Amphetamine이 니코틴성 흥분작용에 의한 카테콜아민 분비작용에 미치는 영향
임건한,서유석,민선영,임지연,김용직,나광문,임동윤 朝鮮大學校 附設 醫學硏究所 2005 The Medical Journal of Chosun University Vol.30 No.1
본 연구의 목적은 d-arphetamine이 흰쥐의 적출부신 관류모델에서 니코틴 수용체 흥분에 의한 카테콜아민(CA) 유리작용에 미치는 영향을 검색하여 그 작용기전을 규명하고자 하였다. D-amphetamine은 흰쥐 부신정맥내로 60분간 관류시 d-amphetamine자체는 약한 CA 분비작용을 나타내었으나, d-amphetamine (30 μM)을 비롯한 강력한 neuronal nicotine 수용체 작용제인 cytisine (50 μM) 및 epibatidine (30 μM)에 의한 CA 유리작용을 처음 4-10분 동안만 유의하게 증강시켰다. 또한, d-amphetamine (30 μM)은 60분간 부신정맥 내로 관류한 상태에서 dihydropyridine L-형 칼슘통로 개방약물인 Bay-K-8644 (10 μM)과 세포질내 칼슘저장고에서 Ca^(2+) ATPase 억제제인 cyclopiazonic acid (10 μM)의 CA 유리작용을 처음 4분간만 유의하게 증강시켰다. 그러나, 고농도의 d-amphetamine (500 μM)은 상기한 모든 분비촉진제의 CA분비작용을 오히려 억제하였다. 이와 같은 연구결과로 보면, 흰쥐 관류 부신수질에서 d-amphetamine은 낮은 농도에서는 콜린성 니코틴 수용체 흥분에 의한 카테콜아민 분비반응을 증강시키지만, 고농도에서는 오히려 억제적으로 작용함을 시사한다. 따라서, d-amphetamine은 용량에 따라서 흰쥐 적출 관류부신수질의 니코틴 수용체의 작용제 및 길항제로 이중 작용(dual action)을 나타내는 것으로 생각된다. 이러한 d-amphetamine의 작용은 흰쥐 부신수질 크롬친화세포의 dihydropyridine계 L-형 칼슘통로의 활성화 및 세포 내 칼슘저장고로부터 칼슘유리작용과 관련성이 있는 것으로 사료된다. The purpose of the present study was to examine the effect of d-amphetamine on CA release evoked by nocotinic receptor stimulation from the isolated perfused model of the rat adrenal gland, and to establish its mechanism of action. D-amphetamine(30 μM), when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced the CA secretory responses evoked by ACh (5.32 mM), nicotine (30 μM), cytisine (50 μM, a selective neuronal nicotinic Nn-receptor agonist) and epibatidine (30 nM, a selective neuronal nicotinic Nn receptor agonist) only for the first period (4~10 min), although it alone has weak effect on CA secretion. Moreover, d-amphetamine (30 μM) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type Ca^(2+) channels, and cyclopiazonic acid, an inhibitor of cytoplasmic Ca^(2+) ATPase only for the first peroid (4 min). However, in the presence rather inhibited the CA secretory responses evoked by the above all of secretagogues. Taken together, these experimental results suggest that d-amphetamine at a low concentration enhances the CA secretion from the rat adrenal medulla evoked by stimulation of cholinergic nicotininc receptors, but at a high concentration it rather inhibits them. It semms that d-amphetamine has dual action acting as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which are might be dependent on the concentration. It is also thought that these actions of d-amphetamine are probably relevant to the activation of the dihydropyridine L-type Ca^(2+) channels located on the rat adrenomedullary chromaffin cell membrane and release of Ca^(2+) from the cytoplasmic store.
임건일,박춘식 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1
Background: Idiopathic interstitial pneumonia(IIP) is histologically divided into usual interstitial pneumonia(UIP), desquamative interstitial pneumonia(DIP), acute interstitial pneumonia(AIP), and nonspecific interstitial pneumonia/fibrosis(NSIP). An alveolitis and a derangement of alveolar wall are prebably followed by fibrosis. In this process, interleukin-6(IL-6), one of proinflammatory cytokines, is presumed to decrease fibrotic reaction. In IIP, NSIP has a better prognosis and a lesser fibrosis than UIP. The purpose of the study was to compare concontrations of IL-6 between UIP and NSIP and define the source of IL-6 synthesis. Method: Six patients with NSIP and 13 patients with UIP were confirmed by open lung biopsy. Bioactivity of IL-6 in bronchoalveolar lavage fluid(BALF) was measured by an bioassay using B9 cell proliferation Spontaneous and lipopolysaccaride(LPS)-stimulated production of IL-6 by BAL cells were compared between two groups. Biopsy specimens from patients with NSIP were freezed and cryosectioned. The tissue slides were fixed in acetone. They were reacted with primary antibodies including anti-IL-6, secondary antibody, and tertiary antibody, in order. The slides stained by immunohistochemistry were obseved by light microscope. Results: 1)Mean concentration of IL-6 of BAL fluid of NSIP group was significantly higher than that of UIP. 2)Spontaneous production of IL-6 by BAL cells of NSIP was significantly higher than that of UIP. 3) Ratio of spontaneous to LPS stimulation in IL-6 production by BAL cells was higher in NSIP than UIP. 4) By immunohistochemistry, IL-6 was strongly stained on interstitial monocytes, interstitial lymphocytes and alveolar epithelial cells, but weakly stained in intraalveolar macrophages. Conclusion; IL-6 production in NSIP was enhanced more than that in UIP. The origin of IL-6 seems to be interstitial cells and the alveolar epithelium and not to be cells present in BALF.