Effect of gamma-aminobutyric acidA receptor agonists and antagonists on the release of enkephalin-containing peptides from dog adrenal gland.

Effect of gamma-aminobutyric acidA receptor agonists and antagonists on the release of enkephalin-containing peptides from dog adrenal gland.
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γ-氨基丁酸A受体激动剂和拮抗剂对狗肾上腺释放含脑啡肽的影响。

DOI:
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发表时间:
1987
期刊:
The Journal of pharmacology and experimental therapeutics
影响因子:
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通讯作者:
I. Hanbauer
I. Hanbauer
中科院分区:
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文献类型:
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作者:
M. Fujimoto;Y. Kataoka;A. Guidotti;I. Hanbauer

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已知肾上腺髓质的嗜铬细胞储存和释放儿茶酚胺、Met 5-脑啡肽(ME)样肽和γ-氨基丁酸(GABA)。本研究的文件,位于犬肾上腺嗜铬细胞膜上的GABAA受体的刺激,引起嗜铬细胞膜的去极化,调节嗜铬细胞内脏神经刺激的反应性。4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇(0.143 mmol/2 ml/min)是一种输注到主动脉囊中的选择性GABAA受体激动剂,可增加ME样肽和儿茶酚胺释放到肾上腺流出血液中。在将GABAA受体阻断剂荷包牡丹碱(0.05 mmol/2 ml/min)输注到主动脉囊中之前,可防止4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇引发的两种物质的释放。两种物质的释放之间存在化学计量关系; 1 nmol/ml血浆中的儿茶酚胺与2 pmol/ml血浆中的ME样肽共同释放。Sephadex G-75柱上的色谱图表明,注射4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇后,各种MW形式的ME样肽释放到肾上腺流出物血液中。当内脏神经的电刺激(10 V/6 Hz)用作刺激时,获得了ME样肽释放的类似曲线。这些数据表明,GABAA受体的直接刺激,导致去极化的嗜铬细胞膜的氯离子通道开放的爆发,并触发神经递质的释放。(250字处删节)
Chromaffin cells of the adrenal medulla are known to store and release catecholamines, Met5-enkephalin (ME)-like peptides and gamma-aminobutyric acid (GABA). The present study documents that stimulation of GABAA receptors located on chromaffin cell membranes of canine adrenal glands, eliciting depolarization of chromaffin cell membranes, modulates the responsiveness of chromaffin cells to splanchnic nerve stimulation. 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol (0.143 mmol/2 ml/min), a selective GABAA receptor agonist infused into the aortic pouch, increases the release of ME-like peptides and catecholamines into the adrenal effluent blood. Prior infusion into the aortic pouch of the GABAA receptor blocker, bicuculline (0.05 mmol/2 ml/min), prevents the 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol-elicited release of both substances. A stoichiometric relationship exists between the release of both substances; 1 nmol/ml of plasma of catecholamines was coreleased with 2 pmol/ml of plasma of ME-like peptides. The chromatographic profile on a Sephadex G-75 column indicates that, after injection of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, various MW forms of ME-like peptides are released into the adrenal effluent blood. A similar profile for the release of ME-like peptides was obtained when electrical stimulation (10 V/6 Hz) of the splanchnic nerve was used as a stimulus. These data suggest that direct stimulation of GABAA receptors causes depolarization of chromaffin cell membranes by a burst of Cl- channel opening and triggers neurotransmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)