Effects of DFP on iridic metabolism and release of acetylcholine and on pupillary function in the rat

Abstract

The time course of the effects of the topical administration of 1μg of diisopropylfluoro-phosphate (DFP) onto the cornea of the rat on the function of the iris and the biochemistry of acetylcholine (ACh) was followed for 6 hr after the acute inhibition of acetylcholinesterase (AChE) in the iris. Pupil diameter was normal at 1 min but from 5 min to 6 hr after DFP, the size of the pupil was less than 50% of control. As measured by infra-red video pupillography, complete miosis occurred within 3.5 to 4.0 min after the application of DFP. From this time on, up to 6 hr, a pupillary light reflex could not be elicited. Acetylcholinesterase activity in the iris was reduced to 36% of control 1 min after the application of DFP, decreased to 8% at 5 min and still remained far below control values at 6 hr. Levels of acetyleholine in the iris were increased by 34% 1 min after the application of DFP and by 54% at 5 min. This increase remained stable for 120 min and then started to return to control values but was still 28% above control at 6 hr. Levels of choline (Ch) in the iris were decreased by 22% 5 min after the application of DFP but quickly returned to normal and were the same as controls at all other times tested. Evidence consistent with the presence of muscarinic presynaptic autoreceptors on cholinergic nerve terminals in the iris of the rat was provided by experiments involving electrically stimulated release of labelled ACh from isolated rat irises. Both DFP (10 −4–10 −6M) and certain concentrations of choline (10 −4M) had an inhibitory effect on the release of ACh that was blocked by scopolamine (10 −6 M). The rat iris is an excellent tissue to use for studying pharmacological agents such as DFP since biochemical parameters can be readily correlated with measurements of physiological function. Moreover, the iris is considerably hardier and longer-lasting than a brain slice and morphologically, it is more homogeneous.