Effect of diisopropylfluorophosphate on muscarinic and gamma-aminobutyric acid receptors in visual cortex of cats.
Administration of diisopropylfluorophosphate (DFP), an organophosphorus (OP) compound, irreversibly inhibits acetylcholinesterase (AChE) and results in cholinergic hyperactivity. This study investigated muscarinic and gamma-aminobutyric acid (GABA) receptor changes in visual cortex of cats following an acute exposure to DFP. A single acute administration of DFP (4 mg/kg) decreased the number of muscarinic receptors at 2, 10, and 20 hours after treatment. GABA receptors were elevated at 2 and 10 hours but returned to within control levels at 20 hours. No significant alteration in muscarinic or GABA receptor affinity was noted. In all cases cortical AChE activity was inhibited 60-90%. These findings show a down regulation of muscarinic receptors after DFP associated with low AChE activity. GABA receptors also are altered, and may be part of a compensatory mechanism to counteract excess cholinergic stimulation.
Townsend
A T
AT
U.S. Army Aeromedical Research Laboratory, Sensory Neurosciences Research Branch, Fort Rucker, Alabama 36362-5292.
Adams
D K
DK
Lopez
J B
JB
Kirby
A W
AW
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002415:Cats; D002800:Cholinesterase Inhibitors; D015536:Down-Regulation; D007531:Isoflurophate / Q000494:pharmacology*; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013223:Statistics as Topic; D014793:Visual Cortex / Q000187:drug effects* / Q000378:metabolism
D002800:Cholinesterase Inhibitors; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D007531:Isoflurophate; D000110:Acetylcholinesterase