Muscarinic receptor binding in mouse brain: Regulation by guanine nucleotides

The effect of guanine nucleotides on the binding properties of muscarinic receptors for cholinergic ligands was studied in several brain regions in mice. In homogenates of medulla-pons and cerebellum, GTP (50 μM) caused and 8 -fold decrease in the binding affinity of agonists but had no effect on antagonist binding. Gpp(NH)p was slightly more potent than GTP. The binding properties of both agonists and antagonists in the cortex and hippocampus were unaltered in the presence of guanine nucleotides. The nucleotide effect on agonists arises mainly from the conversion of high affinity to low affinity binding sites. The possible role of these nucleotides in the mechanism of action of muscarinic receptors is discussed.