The degree of inactivation of the antidiuretic activity of vasopressin by the kidneys and the liver of rats

Abstract

Heller (1937) Heller's (1937) conclusions that 'as the amount of hormone injected is increased the proportion of the hormone which is excreted in the urine decreases'. This would suggest that glomerular filtration might be a contributory factor, as the filtration rate of rabbits would be very small after large doses.More recently it has been found that in rats infused with amounts of vasopressin ranging from 300 to 1500 ,uU/100 g, the antidiuretic activity of the urine was equivalent to 8.1 + 1-23 % of the dose administered (Dicker, 1954).The antidiuretic activity present in the urine was unaffected by the height of the water load, and hence by changes in glomerular filtration or by the rate of urine flow. In hypophysectomized dogs, O'Connor (1951) showed that the rate of excretion of antidiuretic activity in the urine was equivalent to 12 % of the rate at which vasopressin was infused, and was, as in rats, independent of the volume of urine excreted. Finally, in man, the antidiuretic activity of the urine was found to be equivalent to 12-8 % of the amount of vasopressin infused (Noble & Taylor, 1953). There can thus be little doubt that the antidiuretic activity found in the urine could account for only 10 % of the activity of the vasopressin administered. Therefore vasopressin antidiuretic activity is largely destroyed in the body. This paper is concerned with the nature of this inactivation process, and incidentally demonstrates that the small amount of

Inactivation of the antidiuretic activity of vasopressin by tissue homogenates

“…For the assays of antidiuretic activity, rats under ethanol anhesthesia were prepared as described by Dicker & Greenbaum (1954). Their water loads were kept constant during the whole experiment (Boura & Dicker, 1953).…”

“…From the Departments of Pharmacology and Biochemistry, University College, London (Received 11 November 1955) It has been shown in a previous paper that the incubation of vasopressin with kidney or liver slices results in a partial inactivation of its antidiuretic activity (Dicker & Greenbaum, 1954). The present investigation was undertaken with a view to securing more information on the mechanism of inactivation.-A preliminary account of this work has already been published (Dicker & Greenbaum, 1955).…”

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It has been shown in a previous paper that the incubation of vasopressin with kidney or liver slices results in a partial inactivation of its antidiuretic activity (Dicker & Greenbaum, 1954). The present investigation was undertaken with a view to securing more information on the mechanism of inactivation.-A preliminary account of this work has already been published (Dicker & Greenbaum, 1955).

METHODS

Male albino rats of an average weight of 250 g (range: 180-290 g) were used both for the preparation of tissue homogenates and for the antidiuretic assays.

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“…As some of the experiments resulted in the preparation of up to thirty-six samples, these were frozen and stored at -150 C until they could be assayed. Control experiments had shown that preparations frozen at -15°C retained their antidiuretic activities unchanged for periods up to 5 weeks.For the assays of antidiuretic activity, rats under ethanol anhesthesia were prepared as described by Dicker & Greenbaum (1954). Their water loads were kept constant during the whole experiment (Boura & Dicker, 1953).…”

Fate and excretion of the pressor activity of vasopressin in rats

“…From the Department of Pharmacology, University College London (Received 20 February 1957) The fate of the antidiuretic activity of vasopressin has been investigated in experiments in vivo (Burn & Singh Grewal, 1951;Heller, 1952Heller, , 1953 Ginsburg & Heller, 1953;Dicker, 1954;Dicker & Greenbaum, 1954) and in experiments in vitro (Heller & Urban, 1935;Birnie, 1953;Dicker & Greenbaum, 1956). The antidiuretic activity of vasopressin appears to be inactivated by both liver and kidneys though the manner in which the inactivation takes place is still not clear.…”