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The pharmacological properties of cholinergic receptors on the cell body membrane of the fast coxal depressor motoneurone (Df) of the cockroach (Periplaneta americana) have been investigated. Parallel dose-response curves were obtained for the depolarizing actions of four bath-applied agonists, with the following order of effectiveness: nicotine&amp;gt;acetylcholine (ACh), in the presence of 1.0×10−7M neostigmine&amp;gt;carbamylcholine&amp;gt;tetramethylammonium. By contrast, dimethyl-4-phenyl piperazinium, suberyldicholine, D,L-muscarine, oxotremorine, acetyl-β-methylcholine and sebacinylcholine were practically ineffective. Of the three putative receptor-specific ligands used to date in binding studies on insect CNS tissues, α-bungarotoxin (α-BGTX) was much more effective (I50 = 6.4×10−8M) in blocking the depolarization resulting from ionophoretic application of ACh, than either quinuclidinyl benzilate (QNB) (I50 = 1.6×10−4 M) or decamethonium (I50 × 2.8×10−3 M). The order of effectiveness of ligands that were particularly effective in blocking ACh depolarization was α-BGTX&amp;gt;α-cobratoxin (α-COTX)&amp;gt;mecamylamine&amp;gt;dihydro-)β-erythroidine&amp;gt;benzoquinonium. Less potent and almost equally effective were atropine, d-tubocurarine, pancuronium and quinuclidinyl benzilate. Even less effective were hexamethonium, gallamine, decamethonium and succinylcholine, all requiring concentrations of 1.0×10−3M and higher to produce a significant block of the ACh response. Not all reversibly acting antagonists were equally effective in preventing irreversible block of the ACh-induced depolarization by α-BGTX. Whereas α-COTX protected the receptors, mecamylamine did not. With the cell body of Df voltage-clamped, the degree of antagonism of the ACh-induced current was assessed at potentials in the range −120 mV to −60 mV. α-BGTX, dihydro-β-erythroidine, benzoquinonium, QNB and decamethonium appeared to be voltage-independent over this potential range, whereas d-tubocurarine and atropine were strongly voltage-dependent in their blocking actions. Sites of action of cholinergic antagonists at the insect ACh receptor/ion channel complex are discussed.

journal of experimental biology

Actions of Cholinergic Pharmacological Agents on the Cell Body Membrane of the Fast Coxal Depressor Motoneurone of the Cockroach <i>(Periplaneta Americana)</i>

Actions of Cholinergic Pharmacological Agents on the Cell Body Membrane of the Fast Coxal Depressor Motoneurone of the Cockroach (Periplaneta Americana)