Reactions of denervated voluntary muscle, and their bearing on the mode of action of parasympathetic and related nerves

Abstract

A PAPER recently published by one of us with H. W. Dudley [Dale and Dudley, 1929] described the isolation and identification of acetylcholine from the perfectly fresh spleens of certain animals. The occasion of the first chemical recognition of this substance, as a natural constituent of the body, was taken to review the evidence suggesting its connection with certain normal effects of parasympathetic nerves, and also with the contractures produced in denervated voluntary muscles by stimulating parasympathetic and other nerves having, normally, only vasodilator actions. The possibility of explaining this association, between the normal vaso-dilator actions and the effects on motor denervated muscles, by attributing both to the peripheral liberation of a substance having both types of action, had presented itself to several who have worked on these phenomena. It was mentioned by Bremer and Rylant [1924] and again by Hinsey and Gasser [1928]. The view published from this laboratory differed from these only in suggesting acetylcholine, which produces both types of effect with unique intensity, as most likely to be the substance in question. The recent careful review by Gasser [1930] of work on these contracture responses of denervated muscles, from their first discovery by Philip eeaux and Vulpian [1863] to the present day, makes it unnecessary for us to give a connected historical survey; we need only refer, in their proper places, to earlier observations bearing on our own.Gasser, in his review, mentions some difficulties in the way of accepting acetylcholine as the common mediator of these effects, in particular the well-known ease with which the vaso-dilator effect of acetylcholine is obliterated by small doses of atropine, which leave the otherwise similar vaso-dilator effects of the chorda tympani and of PH. LXX.8/'

Observations on an Isolated, Innervated Preparation of Rat Urinary Bladder

“…Another explanation for persisting responses to acetylcholine released from nerves was given by Dale & Gaddum (1930). Their explanation, designated "proximity theory " by Ambache (1955), was that acetylcholine was liberated in such an intimate relationship to the receptor mechanisms that atropine could not prevent its access.…”

On the Pharmacological and Anaphylactic Responsiveness of Denervated Skeletal Muscle of the Guinea‐pig

“…Thus, the denervated diaphragm of the rat fails to develop receptors to either histamine or bradykinin (Boohla & Schachter, 1961) while it is known from the work of Dale & Gasser (1926) and Dale & Gaddum (1930) that denervated gastrocnemius and diaphragm muscles of the cat do not become sensitive to histamine. It should be emphasized, however, that, although histamine has no obvious effects on normal striated muscle, this compound is known to exert a stimulating action on frog's muscle immersed in calcium-poor solution (BUlbring, 1955).…”

Atropine and Micturition Responses by Rats With Intact and Partially Innervated Bladder

“…Accordingly, some fraction of the innervation may be non-cholinergic and there is some evidence which suggests a role for 'purinergic' nerves (Burnstock, 1979). This resistance may however be caused by the inaccessibility of the drug to some of the muscarinic receptors (Dale & Gaddum, 1930;Carpenter, 1977; Elmer, 1978). The release of 0007-1188/81/080837-06 $01.00 high concentrations of acetylcholine from the nerve terminals of the bladder, in close proximity to its postjunctional receptors, may also contribute to atropine resistance (Hukovic et al, 1965).…”