The output per stimulus of acetylcholine from cerebral cortical slices in the presence or absence of cholinesterase inhibition.

1 The release of endogenous acetylcholine (ACh) from cerebral cortical slices stimulated at 0.25, 1, 4, 16 and 64 Hz was measured in the presence either of physostigmine or of physostigmine and atropine.2 Atropine potentiated the evoked release of endogenous ACh especially at low frequencies resulting in an output per stimulus which sharply declined with increasing frequency of stimulation, while in the absence of atropine the output of ACh per stimulus was low and fairly constant.3 The evoked release of [(3)H]-ACh per stimulus following the incubation of the slices with [(3)H]-choline, as estimated by means of rate constants of the evoked release of total radioactivity, showed a frequency dependence similar to endogenous ACh when the two were tested under identical conditions.4 In the absence of an anticholinesterase the evoked release of [(3)H]-ACh per stimulus was dependent on frequency of stimulation in a similar way to that in the presence of physostigmine and atropine.5 Results suggest that under physiological conditions, i.e. in the absence of an anti-cholinesterase, the release of ACh per stimulus decreases with increasing frequency of stimulation and that this decrease is due to a lag in the mobilization of stored ACh rather than in the synthesis of new ACh.