在体内，EEDQ以剂量依赖的方式使大鼠脑5-羟色胺受体失活，但不影响5-羟色胺摄取位点。

In vivo EEDQ dose-dependently inactivates rat brain 5-HT receptors but not 5-HT uptake sites.

作者信息

Pinto W, Battaglia G

机构信息

Neuroscience Graduate Program, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.

出版信息

Neuroreport. 1993 Oct 25;5(1):61-4. doi: 10.1097/00001756-199310000-00015.

DOI:10.1097/00001756-199310000-00015

PMID:8280861

Abstract

The present study investigates the inactivation and recovery of brain serotonin (5-HT) recognition sites by EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2,-dihydroquinoline). Adult male Sprague-Dawley rats were given a single s.c. injection of vehicle (1:1 EtOH/H2O) or EEDQ (1-20 mg kg-1) and sacrificed at 4 h and 7 days (10 mg kg-1 dose) post-injection. EEDQ dose-dependently reduced the Bmax of 5-HT1A(3H-DPAT),5-HT1B(125I-CYP),5-HT2(3H-ketanserin) and 5-HT2/1C(125I-DOI) receptors in cortical homogenates. In contrast, EEDQ was without effect on the 5-HT transporter recognition site (3H-paroxetine). No significant changes in affinity were observed for 5-HT1B, 5-HT2 or 5-HT2/1C receptors. The rank order of sensitivity to EEDQ inactivation was: 5-HT1A > 5-HT1B > 5-HT2 approximately 5-HT2/1C >>> 5-HT uptake sites. This study demonstrates: (1) differential EEDQ inactivation and recovery of 5-HT receptors and (2) lack of EEDQ inactivation of the 5-HT transporter.

摘要

本研究调查了EEDQ（N-乙氧羰基-2-乙氧基-1,2-二氢喹啉）对脑5-羟色胺（5-HT）识别位点的失活和恢复情况。成年雄性Sprague-Dawley大鼠单次皮下注射溶媒（1:1乙醇/水）或EEDQ（1 - 20 mg·kg⁻¹），并在注射后4小时和7天（剂量为10 mg·kg⁻¹）处死。EEDQ剂量依赖性地降低了皮质匀浆中5-HT1A（³H-DPAT）、5-HT1B（¹²⁵I-CYP）、5-HT2（³H-酮色林）和5-HT2/1C（¹²⁵I-DOI）受体的Bmax。相比之下，EEDQ对5-羟色胺转运体识别位点（³H-帕罗西汀）没有影响。5-HT1B、5-HT2或5-HT2/1C受体的亲和力未观察到显著变化。对EEDQ失活的敏感性排序为：5-HT1A > 5-HT1B > 5-HT2 ≈ 5-HT2/1C >>> 5-羟色胺摄取位点。本研究表明：（1）EEDQ对5-HT受体的失活和恢复具有差异性；（2）EEDQ对5-羟色胺转运体没有失活作用。