The uptake of 14C‐neostigmine in the isolated diaphragm was studied after chronic treatment of rats with either neostigmine or diisopropyl fluorophosphate (DFP) and following chronic denervation of the left hemidiaphragm. The uptake was measured as muscle‐to‐medium 14C‐concentration ratio after 3 hours incubation of hemidiaphragms with 3 × 10‐7M 14C‐neostigmine. Subcutaneous injections of neostigmine 150 μg per day for 7 days or DFP 165 μg per day for 10 days to rats weighing 190–220 g resulted in a highly significant increase of 14C‐neostigmine uptake in the isolated diaphragm. Chronic denervation did not affect the 14C‐neostigmine uptake. The results demonstrate that chronic administration of anticholinesterases induce changes in the diaphragm, which result in an increased uptake of 14C‐neostigmine in the isolated muscle.
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