Acute effects of cholinesterase inhibitors on uptake of choline in the rat iris.

The choline uptake system has been characterized in the albino rat iris. The isolated iris of the rat accumulates choline (Ch) by a high affinity (Km = 3.23 microM) and a low affinity (Km = 68.4 microM) process. The uptake of 1 microM Ch at 37 degrees C was inhibited in a dose-dependent manner by hemicholinium (IC50 is 70 microM) and by ouabain (IC50 is 1 mM). The high affinity uptake was temperature and sodium-dependent. At 0 degrees C uptake of Ch was reduced by over 85% and it was not sensitive to hemicholinium. This suggests that choline is taken up by a high affinity active transport into the cholinergic terminals of the iris. The uptake of 1 microM Ch at 37 degrees C was inhibited by 1 mM scopolamine and was reduced in a dose-dependent manner by the irreversible anticholinesterase diisopropylfluorophosphate (DFP). Physostigmine, an anti-cholinesterase lacking agonistic action, decreased the uptake of Ch to 73% of control at 1 mM. The rat iris is a much more homogeneous and readily accessible tissue than the CNS, therefore, it offers several advantages in pharmacological studies of drug action on a selective population of cholinergic terminals.