Binding of some organophosphorus compounds at adenosine receptors in guinea pig brain membranes.
The organophosphorus compounds, sarin, tabun and soman are known to be potent inhibitors of cholinesterase. It was claimed that these agents also interact at neurotransmitter receptor sites. We were unable to detect any interaction at the acetylcholine muscarinic sites; we now focus our attention on the adenosine receptors. Binding studies showed that all three anticholinesterases inhibited the binding of [3H]L-phenylisopropyladenosine ([3H]L-PIA) to the brain adenosine receptors in a dose-dependent manner until receptor concentration became limiting. Soman was found to be 5 and 9 times more effective than tabun and sarin respectively in inhibiting [3H]L-PIA binding. These results suggested that these organophosphorus anticholinesterases could interact directly at the A1 adenosine receptors which could subsequently mediate changes in K+ permeability of synaptic membranes.
Lau
W M
WM
Materials Research Laboratory, Department of Defence, Ascot Vale, Vic., Australia.
Freeman
S E
SE
Szilagyi
M
M
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D007700:Kinetics; D010755:Organophosphates / Q000378:metabolism* / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D012524:Sarin / Q000378:metabolism* / Q000494:pharmacology; D012999:Soman / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D009943:Organophosphorus Compounds; D011983:Receptors, Purinergic; D012999:Soman; D012524:Sarin; C009374:tabun