REACTIONS OF ACETYLCHOLINE RECEPTOR AND ESTERASE STUDIED ON ELECTROPLAX

The effects of various compounds acting on the acetylcholine-receptor or on the acetylcholine-esterase, or on both in the synaptic membrane of the monocellular electroplax preparation have been analyzed. Additional evidence has been obtained that the active sites of these two components are different. Physostigmine, 5 × 10-5 M, potentiates the action of acetylcholine (ACh) to its maximal effect. At higher concentrations of physostigmine the action of ACh is antagonized, thus suggesting that the two compounds compete for the active site of the receptor. In the presence of physostigmine, 5 × 10-5 M, strong spontaneous depolarizations of the membrane are triggered by indirect stimulation of 10 pulses/sec, due apparently to intramembraneous accumulation of ACh. The depolarizing effects of acetyl-, propionyl-, and butyrylcholine are about equally strong, although butyrylcholine is a much poorer substrate of ACh-esterase than the two other esters. Dimethylcarbamate is a more potent receptor activator than monomethylcarbamate. This is in contrast to their strengths as enzyme inhibitors. The depolarizing action of neostigmine has been compared with that of some of its analogs. The potency of these compounds as receptor activators changes in a direction opposite to their strength as inhibitors of ACh-esterase in solution. The d- and l-isomers of acetyl-β-methylcholine do not depolarize the membrane of the electroplax, but act as weak receptor inhibitors. The l-isomer is about 5 times as potent as the d-isomer. The lowest concentration of the d-isomer at which an inhibition of the response to carbamylcholine is observed is 7·5 × 10-4 M. © 1968.