ANTAGONIST AND PARTIAL AGONIST ACTIONS OF D-TUBOCURARINE AT MAMMALIANMUSCLE ACETYLCHOLINE-RECEPTORS

Currents were elicited by acetylcholine (ACh), by d-tubocurarine (dTC) , and by mixtures of ACh and dTC, from stably transformed fibroblasts that express fetal or adult muscle nicotinic receptors, dTC acted as a n antagonist of ACh for activation of adult-type receptors, whereas it acted as a weak partial agonist at fetal-type receptors, The channel- blocking action of dTC was not apparent at the concentrations used, Th e partial agonism could explain previous observations that dTC is less effective at blocking the responses of fetal-type receptors than adul t-type receptors, Binding of dTC to receptors was independently assaye d by measuring the reduction of the initial rate of binding of iodinat ed a-bungarotoxin. Binding of dTC to the two types of receptor was ind istinguishable. The dose-effect relationship for the interaction of dT C and ACh at fetal receptors is consistent with the affinities of dTC measured in binding experiments.