Pharmacologic Properties of Glutamate and GABA (Gamma Aminobutyric Acid) Receptor/Channel Systems

摘要

The GABA(A) receptor was studied by electrophysiologic techniques biochemical methods that detect its binding of radiolabeled ligands, and GABA-induced 36C1-flux. Conductance properties of GABA-activated chloride currents were recorded from cultured hippocampal neurons. The effects on rat brain GABA(A) receptor binding and function, suggested that the GABA(A) receptor was the molecular target for chlorinated hydrocarbon insecticides, which inhibited its binding and function in a stereospecific manner. It was also inhibited by lindane and and type II pyrethroids. On the other hand, it was weakly activated by avermectin B1a. Certain organophosphate anticholinesterases (e.g. soman, triphenyl phosphate, triorthocresyl phosphate, leptophos oxon) also inhibited GABA(a) receptor function but only at relatively higher concentrations, acting on it as a secondary target. Organophosphate anticholinesterases also had pre- and postjunctional effects on locust muscle glutamatergic synapses. DFP and VX, but not tabun, shortened the decay time constant of the glutamate receptor induced current. This occurred as well in presence of phencyclidine. Anatoxin was a more potent agonist that ACh on the skeletal muscle nicotinic acetyl-choline receptor, activating channels with the same conductance as ACh-induced channels but with a shorter lifetime. The ionic channel of the nicotinic ACh receptor was inhibited potently by a component of the venom of Philanthus wasp.