Competitive inhibition of phosphoinositide hydrolysis by the muscarinic receptor antagonist AF-DX 116 is of low affinity in mouse cerebral cortex.

Carbamylcholine stimulated [3H]inositol phosphate accumulation in mouse cerebral cortical slices with an ED50 value of approximately 70 microM. Increasing concentrations of the M2 selective muscarinic cholinergic receptor antagonist, AF-DX 116 (0.3-3.0 microM). produced parallel shifts to the right for concentration-response curves to carbamylcholine. A pA2 value for AF-DX 116 of 6.5 (low affinity) was obtained from Schild plot analysis. It is concluded that the M2 muscarinic receptor subtype, as defined by high affinity [3H]AF-DX 116 radioligand binding, is not appreciably coupled to polyphosphoinositide hydrolysis in the mouse cerebral cortex.