Monoclonal antibodies to purified muscarinic receptor display agonist-like activity.

Abstract

Monoclonal antibody M-35, which immunoprecipitates native calf brain acetylcholine muscarinic receptor, mimics agonist stimulation of the intact guinea pig myometrium; the antibody, just like carbamoylcholine hydrochloride, causes a rise in intracellular cGMP content and an inhibition of cAMP accumulation due to prostacyclin, and it induces uterine contractions. Another antibody, M-23, which reacts with the denatured muscarinic receptor, is devoid of agonist-like activity at the cyclic nucleotide level, but it is still able to induce contractions of both rat and guinea pig myometrium. The cyclic nucleotide changes caused by both carbamoylcholine and antibody M-35 are inhibited by atropine; this antagonist, which blocks carbamoylcholine-mediated contractions, fails to prevent contractions induced by antibodies M-35 and M-23. The information necessary to transmit muscarinic signals is entirely contained in the receptor, and ligands only act to trigger the biological response. The muscarinic receptors of the myometrium are coupled to multiple effector systems.