Guanine nucleotide sensitivity of muscarinic acetylcholine receptors from rat brainstem is eliminated by endogenous proteolytic activity.

The sensitivity to guanine nucleotides of agonist binding to muscarinic acetylcholine receptors was eliminated by incubating rat brainstem membranes at 37 degrees C for 30 min. Pretreatment with any of a variety of proteinase inhibitors prevented this loss of sensitivity. In contrast to other treatments which inactivate guanine nucleotide regulatory mechanisms of muscarinic receptors, incubation at 37 degrees C did not alter agonist binding measured in the absence of guanine nucleotides. Endogenous proteolytic activity appears to inactivate the nucleotide regulatory subunit without engendering its dissociation from the receptor binding subunit.