The muscarinic receptor adenylate cyclase complex of rat striatum: desensitization following chronic inhibition of acetylcholinesterase activity.

Chronic inhibition of acetylcholinesterase activity by treatment with diisopropylfluorophosphate (DFP) decreased the capacity of acetylcholine (ACh) acting at a muscarinic receptor to inhibit basal adenylate cyclase activity in homogenates from rat striatum. There was also a loss of the capacity of ACh to inhibit the activation of adenylate cyclase by dopamine. The desensitization of the muscarinic receptor adenylate cyclase complex was associated with a marked attenuation of the capacity of ACh to stimulate a high-affinity GTPase activity present in striatal membranes. The EC50 value of ACh for inhibiting adenylate cyclase and for stimulating GTPase activity increased following treatment with DFP, while the Hill coefficient for both responses was unaltered.