In vivo EEDQ dose-dependently inactivates rat brain 5-HT receptors but not 5-HT uptake sites.
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.
Pinto
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W
Neuroscience Graduate Program, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Battaglia
G
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020120:Iodocyanopindolol; D007650:Ketanserin / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011804:Quinolines / Q000633:toxicity*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011804:Quinolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D017374:Paroxetine; C000470:EEDQ; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D020120:Iodocyanopindolol; D007650:Ketanserin; D010869:Pindolol