The inhibitory effect of acetylcholine on water diuresis in the dog, and its pituitary transmission

Abstract

RECENT work has made it appear possible that acetylcholine is the effective transmitter of impulses in the central as well as in certain distributions of the peripheral nervous system. Dikshit's work [1934, 1935] first brought this idea into the realm of probability. He injected acetylcholine into the hypothalamus and ventricles of cats and found that the effects produced were similar to those of electrical stimulation of those parts. Later, Chang, Chia, Hsi! & Lim [1937] showed that a reflex secretion of a pressor substance of posterior pituitary origin could be elicited by the stimulation of the central end of the divided vagus nerve. It seemed reasonable, therefore, to try whether acetylcholine' played any part in the liberation of the posterior pituitary hormones, using the inhibition of water diuresis as a test forthe presence of one of the hormones. METHODSBitches were used, in which at a preliminary aseptic operation the fundus of the bladder had been removed to lessen the dead space, and the perineum slit dorsally in order to expose the urethral opening and make catheterization easy. 250 c.c. of water were given by stomach tube every morning as a hydrating dose, and 34 hr. later water diuresis was induced by giving 250-350 c.c. of water according to the size of the dog. The urine was collected and its rate of flow measured by means of a selfretaining catheter leading to a series of graduated tubes. When atropine sulphate was used it was injected subcutaneously in 1-2 mg. doses at the time of the second administration of water. Injections of acetylcholine in a solution of 5 % sodium dihydrogen phosphate were made into the ankle vein with no apparent disturbance of the animal, the volume 1 Molitor & Pick [1924], using dogs, found that choline inhibited water diuresis. They ascribed this effect to a change in water distribution.

Stimuli for the Release of Neurohypophysial Hormones

“…sample in these experiments resulted from the acetylcholine injection. The lack of efficacy of a comparatively high dose of acetylcholine may have been caused by a failure of the acetylcholine to reach the acetylcholine-sensitive areas in the central nervous system (probably in the supraoptic and paraventricular nuclei) activation of which can release ADH (Pickford, 1939(Pickford, , 1947Duke & Pickford, 1951). If so, this could have been the result of anatomical differences in the blood supply of the brain between the rat and the dog because Pickford and her colleagues used dogs.…”

“…The use of atropine has the additional advantage that it prevents the formation of tracheal and bronchial exudate which occurs when ether is used as an anaesthetic. It has been shown by several workers that atropine does not prevent the release of vasopressin (Pickford, 1939;Fang, Liu & Wang, 1962;Mills & Wang, 1964b) although de Wied & Laszlo (1967) All blood samples were taken through polythene cannulae into polythene tubes and injected into the assay animals with plastic syringes to prevent the formation of interfering substances which can occur if blood is stored in glass containers (Bisset & Walker, 1957). Assays of the activity of whole blood samples were started immediately after collection and a four point assay could be completed in about 1 hr.…”

The release of vasopressin by nicotine: further studies on its site of action.

“…The site of this vasopressin releasing action of nicotine has not been subject to controversy until quite recently. Pickford (1939) demonstrated that acetylcholine induces an antidiuretic response in atropinized dogs and that this response is absent in animals with experimental diabetes insipidus. Subsequently Pickford (1947) and Duke, Pickford & Watt (1950) showed that the neurones in the supraoptic nucleus exhibit nicotinic-like receptors.…”

“Water Diuresis” Produced During Recumbency by the Intravenous Infusion of Isotonic Saline Solution 1

“…Many stimuli, in addition to hypertonicity, increase ADH production, including certain anaesthetic (1) and narcotic drugs (2), barbiturates (3), smoking (4,5) and nicotine (6, 7), acetylcholine (8), exercise (9), emotion (9), syncope ( 10), pain ( 11 ) and conditioned reflexes ( 11 ), as well as the direct electrical (12) or acetylcholine (13) stimulation of nerve cells and fibers connected with the pars nervosa of the pituitary gland. Removal of amounts of blood insufficient to alter blood pressure significantly may nevertheless lead to increased ADH activity (9).…”