THE SITE AND MECHANISM OF THE CONTROL OF CHOLINERGIC SENSITIVITY

¹ Department of Ophthalmology Research, College of Physicians and Surgeons, Columbia University, New York

Chronic topical anticholinesterase (anti-ChE) treatment of the eye decreases the miotic effectiveness of the anti-ChE agent itself and causes a marked subsensitivity to the miotic effects of cholinomimetic drugs. Parasympathetic denervation of the eye eliminates the miotic effects of anti-ChE agents and renders the iris supersensitive to cholinomimetics. Chronic anti-ChE treatment has no measurable effect on the sensitivity of parasympathetically denervated eyes to carbachol and piocarpine and facilitates rather than decreases their sensitivity to methacholine. Cholinergic subsensitivity can be induced in parasympathetically denervated eyes when a continuous local supply of acetyicholine is provided in these eyes by daily intravitreal deposition of acetylcholine throughout the period of pretreatment with the anti-ChE agent. Repeated intravitreal injections of hemicholinium-3 into normally innervated eyes leads to a partial supersensitivity to cholinomimetics, or minimizes the anti-ChE-induced subsensitivity. Reduction of central parasympathetic outflow to the iris by light deprivation prior to and throughout the anti-ChE treatment also minimizes the development of subsensitivity. Similar stimulus deprivation without anti-ChE treatment leads to the development of a partial supersensitivity to miotics which is somewhat lesser in extent than denervation supersensitivity. Exposure of cats to environmental lighting conditions of higher than normal intensity results in a pronounced shift to the right in the pilocarpine dose-response curve. It is concluded that the sensitivity of the iris sphincter to cholinomimetics is a continuous function which is controlled by the long-term local concentration of acetylcholine at the site of the target organ.

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				L. Z. Bito, M. J. Dawson, and L. Petrinovi\l=c`\ Cholinergic Sensitivity: Normal Variability as a Function of Stimulus Background Science, May 7, 1971; 172(3983): 583 - 585. [Abstract] [PDF]