SUPPRESSION OF GABA(B) RECEPTOR FUNCTION IN RAT NEOCORTICAL SLICES BYAMILORIDE

Interactions of amiloride with GABA(B) receptors have been examined us ing spontaneously discharging rat neocortical slices. These discharges were suppressed by the GABA(B) receptor agonist baclofen (10 mu M), a nd were prevented by amiloride and its analogs 5-(N,N-dimethyl)-amilor ide, 5-(N-methyl-N-isobutyl)-amiloride and benzamil, but not by triamt erene (100-500 mu M). Each of these also increased the spontaneous dis charge rate and reduced the discharge amplitude. The action of amilori de and its analogs in preventing the action of baclofen, may involve a llosteric modification of the receptor binding sites via guanine nucle otide-binding proteins, or an indirect effect through antagonism of co -activated adenosine A(1) receptors.