Release of acetylcholine at the motor endplate of the rat — evidence against a muscarinic acetylcholine autoreceptor

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Abstract
1 The effect of some drugs on the release of endogenous acetylcholine from the phrenic nerve-hemidiaphragm preparation of the rat was measured. Muscarinic ligands had no effect. 8-Br-cyclic GMP, a penetrating analogue of cyclic guanosine 3′,5′-monophosphate (cyclic GMP) was also without effect. 8-Br-cyclic AMP somewhat enhanced the basal release while the potassium-induced release remained unaltered. 2 In supersensitivity experiments, no specific binding of ligand [3H]-quinuclidinylbenzilate ([3H]-QNB) was found in homogenates of the diaphragm, either before or after atropine treatment, while concomitant binding studies in the CNS demonstrated the expected increase in muscarinic binding sites after atropine. 3 Our conclusion is that muscarinic acetylcholine receptors are probably absent from the presynaptic motor endplate area of the rat. Certain preliminary results suggest that a presynaptic nicotinic mechanism might be involved in the release of acetylcholine.