Observations on the action of acetylcholine and adrenaline on the hypothalamus

Abstract

O'Connor & Verney (1945) and Verney (1947) showed that in dogs the inhibition of water diuresis resulting from an emotional stimulus was of two types, a rapid inhibition which could be abolished by section of the splanchnic nerves and denervation of the kidneys and suprarenals, and a slow inhibition due to the release of the antidiuretic hormone from the posterior lobe of the pituitary. The slow inhibition could be prevented by the injection intravenously of adrenaline i min. before the application of the emotional stimulus. These and other observations led them to the conclusion that adrenaline in some way prevented the release of the antidiuretic hormone, but not its action on the kidneys, i.e. that it acted centrally.Some observations made by Pickford (1939Pickford ( , 1947, and Duke, Pickford & Watt (1950) have shown that intravenously administered acetylcholine (ACh) in unanaesthetized atropinized dogs leads to the liberation of antidiuretic hormone, probably by an action on the supraoptic nuclei. It seemed worth testing whether adrenaline could prevent the ACh-induced release of the antidiuretic hormone, and the following observations were made with this object in view. METHODSTrained dogs, after hydration and during water diuresis, were given intravenous injections of adrenaline chloride and ACh HCI dissolved in 1 ml. 0 9 % NaCl solution. The doses of adrenaline varied from 5 to 30 pg. and those of ACh from 0 5 to 3 mg. The drugs were injected either mixed in the syringe immediately before use, or the adrenaline was given 5-35 sec. before the ACh. In the latter case the needle was left in the malleolar vein and the syringe changed. The volumes of urine excreted over short intervals oftime both before and after the injections were noted. Ifthe duration of the diuresis allowed, the response to the mixed drugs was tested between two responses to ACh alone, or the injection of ACh was placed between two injections of the mixed drugs. Sometimes there was time for only two injections in the course of a water diuresis. Occasionally a second dose of water was given so that further responses could be observed at least on the same day. On three occasions measurements were made of the clearances of creatinine and diodone on urine samples collected over short intervals of time.Of the thirteen dogs on which observations were made, six had had their kidneys denervated by stripping the renal pedicle and dividing the capsule from all abdominal connexions.

The Effects of Drugs on the Release of Vasopressin

“…Ethopropazine with a two carbon side chain, a side branch and ethyl groups on the terminal nitrogen, causes some release and a partial blockade of subsequent release by haemorrhage. Promethazine, however, with a two carbon side chain, a branch on the side chain and methyl groups on (1939,1947), Duke & Pickford (1951) and Duke, Pickford & Watt (1950).) This hypothesis is consistent with the suggestion of Feldberg (1950) Todrick (1954) demonstrated, some have anticholinesterase activity.…”

“…Table 5 shows that in four out of four experiments, chlorpromazine did prevent the excitatory effects of promethazine. The work of Pickford et al (Pickford, 1939(Pickford, , 1947Duke & Pickford, 1951;Duke, Pickford & Watt, 1950) strongly suggests that the nervous mechanism for the release of neurohypophysial hormones is cholinergic. Pickford and her co-workers, Fang, Lin & Wang (1962) and Mills & Wang (1964b) found, however, that atropine did not prevent the release of vasopressin.…”

“…Drugs were chosen which antagonize the action of acetylcholine, adrenaline and noradrenaline, 5-hydroxytryptamine and histamine because there is good circumstantial evidence that these substances may be chemical transmitters in the central nervous system (Crossland, 1960). Adrenaline, noradrenaline and ethanol were also investigated because of the reports that these compounds affect the release of neurohypophysial hormone (O'Connor & Verney, 1945;Verney, 1947;Duke & Pickford, 1951;Ames & van Dyke, 1952;Dicker, 1958;Chaudhury, 1961;Fuchs, 1966).…”

A microinjection study of the control of antidiuretic hormone release by the supraoptic nucleus of the hypothalamus in the cat

“…is affected by a blood-brain barrier (Bertler, Falck, Owman & Rosengren 1966). Adrenaline has been found to inhibit ADH secretion (O'Connor & Verney, 1945;Abrahams & Pickford, 1956), but also to reinforce the antidiuretic action of acetylcholine (Duke & Pickford 1951). Dual action of catecholamines has been observed in autonomic ganglia both with respect to dose (Bulbring 1944) and to the level of ganglionic stimulation (Elliott 1965).…”

The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs

“…This possibility is considered by Duke & Pickford (1951) in their work on the interference of adrenaline with the stimulation of the supraoptic nuclei by acetylcholine. A modifying influence of adrenaline on transmission at spinal cholinergic synapses has been convincingly demonstrated (Biilbring & Burn, 1941;Stavraky, 1947).…”