Inactivation of 5-HT1A and [3H]5-HT binding sites by N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ) in rat brain.
Inactivation of 5-HT1A and [3H]5-HT binding sites by N-Ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ) was studied in regions of rat brain. After exposure to EEDQ (4 mg/kg body wt.) for 7 days, it is observed that the density of 5-HT1 receptor sites was decreased by nearly 20% in both cortex and hippocampus. The decrease, however, in 5-HT1A sites was more significant (70%) in both the regions. The affinity of [3H]5-HT to 5-HT1 sites was decreased significantly in both cortex and hippocampus after exposure to EEDQ, without affecting the Kd of 5-HT1A sites. Displacement studies suggested that EEDQ has high affinity to 5-HT1 sites with a Ki of 42.9+/-2.4 nM. After exposure neither basal nor 5-HT stimulated adenylyl cyclase activity was changed in cortex. The results of this study suggest that EEDQ decreases the density of 5-HT1 and 5-HT1A receptor sites but does not cause functional downregulation of these sites in rat brain.
Subhash
M N
MN
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Srinivas
B N
BN
Vinod
K Y
KY
Jagadeesh
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014316:Tritium
D011804:Quinolines; D012702:Serotonin Antagonists; D014316:Tritium; D012701:Serotonin; C000470:EEDQ; D000262:Adenylyl Cyclases