The sympathomimetic effect of acetylcholine on the spleen of the cat

Abstract

Evidence has accumulated that acetylcholine (ACh) is capable of acting on neurones at sites other than the subsynaptic membrane. It has been shown for instance that it can excite mammalian sensory nerve fibres in the skin and mesentery (Brown & Gray, 1948;Douglas & Gray, 1953), carotid sinus pressure receptors (Diamond, 1955) and C fibres carrying activity from cutaneous touch receptors (Douglas & Ritchie, 1960). Among the first to suggest that acetylcholine might excite post-ganglionic sympathetic fibres were Coon & Rothman (1940), who injected acetylcholine into the skin and obtained sympathetic effects which were prevented by ergotamine and by degeneration of the sympathetic supply to the area. Recently, Brandon & Rand (1961) and Daly & Scott (1961) have reinvestigated the sympathomimetic effect of acetylcholine on the spleen, previously described by Farber (1936). They showed that close arterial injection of acetylcholine into the spleen produced contraction of that organ and this effect could be prevented by reserpine, by adrenergic blocking agents, by hexamethonium and by degeneration of the sympathetic supply. It seemed possible that this sympathomimetic effect of acetylcholine might be due to its exciting the sympathetic post-ganglionic adrenergic C fibres, and experiments were carried out to test this hypothesis. Some of the results of these experiments have already been communicated to the Physiological Society (Ferry, 1962). METHODSCats were anaesthetized with ethyl chloride and ether and then with intravenous chloralose, 80 mg/kg. The abdominal cavity was opened by a mid-line incision and the spleen and its arterial supply were separated from the stomach and omentum by tying and cutting the hepatic, left gastric and gastro-epiploic arteries. In some experiments the stomach was removed to gain better access to the arterial supply of the spleen.Acetylcholine solution was injected into the splenic artery through a polythene cannula placed in a suitable sidebranch and pointing toward the heart. The arteriesused for retrograde cannulation were the hepatic artery, the smaller of the two divisions of the splenic artery, or a small branch of the splenic artery just before it enters the spleen. In one experiment one of the gastro-epiploic arteries was used. The arrangement of the cannula was such that injections could be made without interrupting the natural blood supply during the injection.

Pharmacology of the Antihypertensive Guanoxan

“…Reiner-(1960) reported that of the common sympathomimetic amines (±)-amphetamine, dext amphetamine and methylamphetamine alone produced depolarization and block in the cat superior cervical ganglion. The demonstration by Ferry (1963) that acetylcholine excites the nerve endings of sympathetic postganglionic adrenergic C fibres suggests that dexamphetamine also may act (in a fashion similar to its action on the subsynaptic membrane) at other sites in adrenergic neurones. Boura & Green (1963) have drawn an analogy between the effects of adrenergic neurone blocking agents in preventing release of catechol amines and their local anaesthetic action.…”

A possible role of the glomus cell in controlling vascular tone of the carotid labyrinth of Xenopus laevis.

“…Hatakeyama and Kato (1958, 1959, 1960 reported that a great deal of vascularity of amphibians was usually constricted by Ach, and they attributed this to the release of Ach at sympathetic nerve terminals. Ferry (1963) reported that high dose of Ach excited the sympathetic post ganglionic nerves somewhere near their endings and this was not affected by Atr, but was abolished by C6 administration.…”

The Sympathetic Postganglionic Fibre and the Block by Bretylium; The Block Prevented by Hexamethonium and Imitated by Mecamylamine

“…He concluded that acetylcholine excited the sympathetic postganglionic nerves to the spleen somewhere near their endings. Since Daly & Scott (1961) had found that hexamethonium did not abolish the contraction of the spleen caused by stimulating the splenic nerves, Ferry (1963) concluded that his observation explained why acetylcholine acted like sympathetic stimulation. He inferred that this action did not imply the existence of a cholinergic link between the nerve impulse and the release of noradrenaline.…”

“…One of the observations pointing to this -concept was that acetylcholine, in the presence of atropine, acted like sympathetic stimulation in many organs. Ferry (1963) has recently found that the injection of acetylcholine into an artery leading to the spleen caused a centripetal discharge in the C fibres of the splenic nerves, and that this discharge was abolished by hexamethonium. He concluded that acetylcholine excited the sympathetic postganglionic nerves to the spleen somewhere near their endings.…”