Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors.
[3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, [3H]flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors.
Churchill
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Department of Anatomy, University of Kansas Medical Center, Kansas City 66103.
Pazdernik
T L
TL
Cross
R S
RS
Nelson
S R
SR
Samson
F E
FE
D000818:Animals; D001345:Autoradiography; D003975:Diazepam / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D012999:Soman / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014316:Tritium; D014741:Video Recording
D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D014316:Tritium; D005445:Flunitrazepam; D011813:Quinuclidinyl Benzilate; D012999:Soman; D003975:Diazepam; D007608:Kainic Acid