Cholinergic activity of intestinal musclein vitro taken from horses with and without equine grass sickness

Abstract

Equine grass sickness (EGS) is a pan-dysautonomia of horses that involves central and peripheral neuronal degeneration and ultimately depletion. This is the first reported functional study on the motility of equine intestine taken immediately post mortem from horses with EGS. Strips of smooth muscle from the small intestine of healthy and EGS-affected horses were suspended in an organ bath and their motility was measured isometrically. The activity of the cholinergic system was studied. Physostigmine enhanced the motility of all muscle strips. Tissues taken from horses suffering from acute grass sickness (AGS) had the longest latency before a measurable response could be obtained (p < 0.05). The ileum appeared to be damaged by EGS to a greater extent than the duodenum. For the duodenal strips the enhanced rate of spontaneous contractions was significant (p < 0.05) for both normal tissue and that affected by grass sickness but this was not the case for the ileal strips. Muscarinic receptor sensitivity investigation using bethanecol suggested a hypersensitivity of receptors with AGS material.

The Pharmacology of Physostigmine

“…Some evidence suggests a neurochemical link to amyloid processing and, in particular, a role for cholinergic innervation. It was early recognized that a common characteristic shared by the several neuronal groups demonstrating Alzheimer pathology was the presence of AChE (24,64,173,184). This hypothesis is of particular interest since it links the two current major hypotheses of Alzheimer dysfunction -neuronal acetylcholine loss and amyloid deposition -and provides additional rationale for cholinergic replacement therapy.…”

“…The effects of physostigmine have been examined experimentally in a variety of memory paradigms, passive, active, and those induced by cholinergic deficits and lesions. These effects have been reviewed (81,184).…”

“…The central cholinergic nervous system has long been associated with learning and memory in both humans and animals (24,73,74,184). The effects of physostigmine have been examined experimentally in a variety of memory paradigms, passive, active, and those induced by cholinergic deficits and lesions.…”

The neurology and enterology of equine grass sickness: a review of basic mechanisms

“… 63 There is no explanation for the apparent susceptibility of the ileum, although it has been suggested that the putative neurotoxin might be absorbed preferentially in this region 61 . There is reduced release of acetylcholine in vitro in tissues taken from cases of acute EGS, particularly in ileal preparations 65 and a good correlation between functional cholinergic responses in vitro and enteric neuronal morphology 64…”

Role of Acetylcholinesterase Inhibitors and Alzheimer Disease

“…[67][68][69][70][71][72] Physostigmine exerts a stereoselective inhibition by acting as a pseudosubstrate and transferring a carbamate residue to the enzyme's active site.…”