Unmasking, After Cholinergic Paralysis by Botulinum Toxin, of a Reversed Action of Nicotine on the Mammalian Intestine, Revealing the Probable Presence of Local Inhibitory Ganglion Cells in the Enteric Plexuses

Abstract

There are several indications that the motor nerves to the intestine are susceptible to the paralysing action of botulinum toxin. Dickson and Shevky (1923) noticed a distinct interference with the intestino-motor function of the vagus in their experiments on cats; and most accounts refer to the obstinate constipation which is a prominent feature of human botulism.The present experiments, conducted on mice and rabbits, aim at demonstrating this condition in isolated intestinal preparations. In mice systemic botulism was produced, and peristaltic activity was studied in surviving portions of the intestine. In rabbits the toxin was injected locally into the wall of an intestinal segment, which was examined later after the death of the animal from a spread of intoxication. Further information was gained by studying the response of these poisoned segments to nicotine; with this drug it is possible to stimulate the same ganglion cells in the intestine as are involved in the mediation of peristaltic reflex activity, and the extinction of the motor response to nicotine can therefore be used equally well as an index of the paralysis in the myenteric plexus.Botulinum toxin has a selective affinity for cholinergic nerve endings, and produces effects resembling denervation (Guyton and MacDonald, 1947;Ambache, 1949Ambache, , 1951. It is generally assumed that the nerve fibres originating from the cells of the myenteric plexus are cholinergic. These motor neurones should therefore also succumb to the paralytic action of this toxin, and should cease to respond to nicotine-stimulation of their ganglion cells. It has been found that, when the action of nicotine on these motor neurones is paralysed by botulinum toxin, an opposite action of nicotine is unmasked at the same time, revealing a stimulation of ganglion cells which are inhibitory, and appear to be the cell bodies of short adrenergic neurones. METHODSBotulinum toxin.-For the experiments on mice, which were performed in 1949 in Guy's Hospital Medical School, a type A toxin broth was used. It was kindly supplied by Dr.

Pharmacological Responses of the Isolated Innervated Intestine and Rectal Caecum of the Chick

“…In the rectal caecum relaxations produced by nicotine were much more marked. Relaxations produced by ganglion stimulants in intestinal preparations are well known (Kuroda, 1917;Ambache & Edwards, 1951;Ambache, 1951;Evans & Schild, 1953;Jarrett, 1962;Greeff, Kasperat & Osswald, 1962;Weiss, 1962;Burn & Gibbons, 1964;Bucknell & Whitney, 1964;Fishlock & Parks, 1966;Burnstock, Campbell & Rand, 1966). Such relaxations produced by nicotine in preparations from other species are usually revealed or potentiated in the presence of atropine, but in the chick gut the contractile action of nicotine, TMA and DMPP were often resistant to the blocking action of atropine and hyoscine, and little or no potentiation of the relaxations occurred.…”

The effects of acetylcholine on the volume and vascular resistance of the dog's spleen

“…DE BURGH DALY AND MARY J. SCOTT There is some evidence in favour of the view that the nicotine-like action of acetylcholine on the spleen is the result of stimulation of peripheral ganglion celLs situated in the vascular bed of the splenic artery. Ambache (1951) has suggested that the inhibitory action of nicotine on the intestine might be due to stimulation of local adrenergic ganglion cells, since it was abolished by hexamethonium and by large doses of nicotine. We have shown that, in atropinized spleen preparations, (1) the acetylcholine contraction of the spleen is potentiated by anticholinesterases and is abolished by hexamethonium; (2) ganglion-stimulating drugs such as nicotine and DMPP cause contraction of the spleen, which is also abolished by hexamethonium, and by anti-adrenaline drugs such as dibenzyline or dibenamine.…”

Acetylcholine release from guinea‐pig ileum by parasympathetic ganglion stimulants and gastrin‐like polypeptides

“…However, it was shown that drugs like atropine, hexamethonium, tetrodotoxin, adrenaline or cooling (Ambache, 1951;McDougal & West, 1954;Day & Vane, 1963;Daniel, 1966;Gershon, 1967) can inhibit, and anticholinesterases can potentiate the action of nicotine-like drugs on the intestine, and it was suggested that their action is mediated through acetylcholine release. Paton & Zar (1968) presented additional evidence for the indirect action of nicotine-like substances; nicotine and DMPP failed to produce contractions in denervated smooth muscle.…”