阿法沙龙增强并模拟了γ-氨基丁酸（GABA）在豚鼠离体回肠中诱导的收缩反应。

Alfaxalone potentiates and mimics GABA-induced contractile responses in the guinea-pig isolated ileum.

作者信息

Ong J, Kerr D I, Johnston G A

机构信息

Department of Pharmacology, University of Sydney, New South Wales, Australia.

出版信息

Br J Pharmacol. 1988 Sep;95(1):33-8. doi: 10.1111/j.1476-5381.1988.tb16545.x.

DOI:10.1111/j.1476-5381.1988.tb16545.x

PMID:3219474

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1854129/

Abstract

Alfaxalone (1-100 nM) potentiated gamma-aminobutyric acidA (GABAA)-receptor-mediated contractile responses in the guinea-pig isolated ileum, with a leftward shift of the GABA concentration-response curve, and a significant potentiation of the GABA-induced contractions over the lower concentration-range for GABA (3-30 microM). Alfadalone on the other hand, did not affect contractile responses to GABA. 2. Picrotoxinin (10 microM) induced a non-parallel rightward shift of the GABA concentration-response curve, with a 50% depression of the maximum response to GABA. Alfaxalone (100 nM) potentiated the responses to GABA in the presence of picrotoxinin (10 microM) over the GABA concentration-range of 10-100 microM, causing a leftward shift of the concentration-response curve, but without affecting the depression of the maximum response by picrotoxinin. 3. Bicuculline methochloride (10 microM) caused a parallel rightward shift of the GABA concentration-response-curve; the ratio of this shift was unchanged in the presence of alfaxalone (100 microM), although the latter itself displaced the curve leftwards. 4. Alfaxalone (1-100 mM) also induced a similar potentiation of contractile responses to 3-amino-1-propanesulphonic acid (3-APS), a GABA agonist not subject to uptake. Such concentrations of alfaxalone were ineffective against contractile responses to exogenous acetylcholine. 5. Higher concentrations of alfaxalone (1 microM and above), however, elicited a GABA-like ileal contraction, sensitive to both picrotoxinin (10 microM) and bicuculline (10 microM). 6. In conclusion, alfaxalone potentiated GABAA-receptor-mediated contractile responses in the guinea-pig isolated ileum by acting at a modulatory site on GABAA-receptor-chloride-ionophore complexes of GABA-sensitive myenteric neurones, whilst high concentrations of alfaxalone exhibited a GABA-mimetic action at GABAA-receptors in the ileum. It is suggested that more than one site may exist where steroids interact with the GABAA-receptor-ionophore complexes.

摘要

阿法沙龙（1 - 100纳摩尔）增强了豚鼠离体回肠中γ-氨基丁酸A（GABAA）受体介导的收缩反应，使GABA浓度-反应曲线向左移位，并且在较低GABA浓度范围（3 - 30微摩尔）内显著增强了GABA诱导的收缩。另一方面，阿法多龙不影响对GABA的收缩反应。2. 苦味毒（10微摩尔）使GABA浓度-反应曲线发生非平行向右移位，使对GABA的最大反应降低50%。在存在苦味毒（10微摩尔）的情况下，阿法沙龙（100纳摩尔）在10 - 100微摩尔的GABA浓度范围内增强了对GABA的反应，导致浓度-反应曲线向左移位，但不影响苦味毒对最大反应的抑制作用。3. 甲氯双氢荷包牡丹碱（10微摩尔）使GABA浓度-反应曲线平行向右移位；在存在阿法沙龙（100微摩尔）的情况下，该移位比例不变，尽管后者本身使曲线向左移位。4. 阿法沙龙（1 - 100毫摩尔）也诱导了对3 - 氨基-1 - 丙烷磺酸（3 - APS，一种不易被摄取的GABA激动剂）收缩反应的类似增强。这种浓度的阿法沙龙对外源性乙酰胆碱的收缩反应无效。5. 然而，更高浓度的阿法沙龙（1微摩尔及以上）引发了类似GABA的回肠收缩，对苦味毒（10微摩尔）和荷包牡丹碱（10微摩尔）均敏感。6. 总之，阿法沙龙通过作用于对GABA敏感的肌间神经元的GABAA受体-氯离子载体复合物上的调节位点，增强了豚鼠离体回肠中GABAA受体介导的收缩反应，而高浓度的阿法沙龙在回肠的GABAA受体上表现出GABA模拟作用。提示类固醇与GABAA受体-离子载体复合物相互作用可能存在不止一个位点。