Effects of eserine and neostigmine on the interaction of α bungarotoxin with Aplysia acetylcholine receptors

Binding of [¹²⁵]α bungarotoxin to acetylcholine receptors of ganglionic homogenate of the marine mollusc Aplysia is blocked by he anticholinesterases eserine (I₅₀ = 4 μM) and neostigmine (I₅₀ = 0.2 mM). The classical acetylcholine antagonist d tubocurarine blocks with an I₅₀ of 2 μM. Eserine (I₅₀ = 3.2 μM) and neostigmine (I₅₀ > 1 mM) also block toxin binding to a solubilized receptor preparation. In contrast to their relative potency in blocking toxin binding, neostigmine is a more potent inhibitor of Aplysia acetylcholinesterase (I₅₀ = 14 nM) than is eserine (I₅₀ = 250 nM). α Bungarotoxin does not affect esterase activity or interfere with the ability of eserine to block the esterase. The response to acetylcholine recorded through intracellular microelectrodes is blocked by α bungarotoxin. Neither eserine nor neostigmine blocks the acetylcholine response; rather, they prolong and increase it, as expected from their effects on the esterase. Eserine (0.1 mM) blocks the α bungarotoxin inhibition of the physiological acetylcholine response. These results indicate that eserine and neostigmine block the binding of α bungarotoxin by interacting with a site which is different from both the esterase and the cholinergic sites of the acetylcholine receptor.