1. In order to determine the role of acetylcholine (ACh) transmission in neurotrophic regulation of muscle cholinesterase (ChE), the effects of botulinum toxin treatment were compared with those of denervation, in terms of two fractions of muscle ChE. The sternocleidomastoid muscles of rats were either denervated or injected with botulinum toxin. After 7 days the muscles were frozen, and sequential sections were assayed for acetylcholinesterase activity. By this method, the ChE activity of end‐plates (EPChE) and non‐end‐plate regions (background ChE, BChE) were separately determined. 2. The background ChE was reduced to the same extent by botulinum toxin and denervation. This is interpreted to mean that the neurotrophic regulation of BChE may be wholly cholinergic. 3. The EPChE was significantly reduced by both treatments, but the effect of botulinum toxin was only half as great as that of denervation. This indicates that EPChE is only partially regulated by ACh transmission. The larger effect of denervation suggests that some non‐cholinergic influence may be operating in this situation as well. Disruption of the structural integrity of the end‐plate, with consequent loss of binding sites for the ChE, may account for the additional effect of denervation.
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