Identification of the Stable Antidiuretic Substance (“Stable Ads”) of Serum With 5‐hydroxytryptamine

Abstract

Rat serum contains, according to Ginsburg and Heller (Ginsburg and Heller, 1951;Heller, 1952; Ginsburg and Heller, 1953), two antidiuretic factors. The first, called " unstable antidiuretic substance " (" unstable ADS "), disappears on standing and is most abundant in heart or jugular serum that is, in serum obtained from blood returning from the head: its posterior pituitary origin seems probable. The second factor, provisionally called " stable antidiuretic substance" (" stable ADS "), is not inactivated on standing, is found in arterial serum, seems to originate during coagulation-the same amount of plasma tested by the same method did not modify urine flow significantly-and to manifest its antidiuretic action only when injected subcutaneously (Ginsburg and Heller, 1953): its origin and nature are uncertain.On the basis of unpublished observations, Ginsburg and Heller (1950) reported that they were unable to identify the " stable ADS " with 5-hydroxytryptamine (serotonin, enteramine).This seemed surprising, since all the characteristics of the " stable ADS" noted above are shared by 5-hydroxytryptamine. Moreover, rat serum, in which " stable ADS" was first found, contains quantities of 5-hydroxytryptamine which are sufficient to influence the diuresis of hydrated rats. In fact the average 5-hydroxytryptamine content of rat serum is 0.97 Lg./ml. (Erspamer and Faustini, 1953) and the minimum antidiuretic dose of this substance, by the subcutaneous route, is 0.4 ,g. per 100 g. of body weight (Erspamer and Ottolenghi, 1953).When given intraperitoneally 5-hydroxytryptamine is 5 to 10 times less effective than when injected subcutaneously (Erspamer and Ottolenghi, 1953). Ames and Van Dyke (1952) found that 4 or 6 &g.serotonin given intravenously had no antidiuretic effect in rats.The experiments now to be described were designed to determine whether 5-hydroxytryptamine is identical with Ginsburg and Heller's " stable ADS." METHODS Blood was obtained by decapitation, except in dogs and in man, when it was taken from the femoral artery or from the antecubital vein. After collection it was kept for 2 to 3 hours at room temperature and then for a further 15 to 20 hours in a refrigerator. The serum was separated by centrifugation.Serum samples were obtained from 20 human beings, 15 rats, 10 rabbits, 3 dogs, 3 cats, 2 goats, and 10 hens.In some experiments native serum was compared with acetone extracts of serum, but in most experiments acetone extracts only were studied. To prepare these extracts, serum was treated with 4 volumes of acetone, was left standing overnight in the refrigerator and then filtered. The solvent was evaporated under reduced pressure just before use, and was then brought to the desired volume with distilled water. The acetone extracts keep indefinitely and thus offer homogeneous material for several successive experiments.Estimations of antidiuretic activity were made on unselected adult albino rats of both sexes, weighing from 150 to 270 g. In all, 180 groups of four animals each were used. Two...

The estimation of vasopressin in the blood and urine of hydrated and dehydrated subjects

“…These authors used the hydrated rat as the assay preparation, but their methods cannot be regarded as valid for the quantitative assay of vasopressin because serum was used and the injections were administered either subcutaneously or intraperitoneally. Measurements of antidiuretic activity will vary according to the route of injection (Noble, Rinderknecht & Williams, 1939; Dicker, 1953;Ginsburg & Heller, 1953;Erspamer & Sala, 1954) and, unless the intravenous route is used, the true values may be greatly enhanced (Ames & van Dyke, 1952;Lewis, 1953;van Dyke, Adamsons & Engel, 1955). Furthermore, the use of serum is illogical, since it inactivates vasopressin (Dicker & Ginsburg, 1950;Ames & van Dyke, 1952;Heller, 1952).…”

Metastatic Argentaffinoma Secreting 5-Hydroxytryptamine in a Patient with a Patent Foramen Ovale

“…Ann Evidence has recently accumulated that 5-hydroxytryptamine (5-H.T.) is a specific product of the enterochromaffin cell (Barter and Pea rse, 1953;Erspamer, 1954), and many of the signs and symptoms associated with carcinoid tumours seem to be directly attributable to the release of large amounts of this substance into the circulation (Page, 1958). There are, however, some facts which are not readily explicable in terms of 5-H.T.…”

“…has been questioned by Abrahams and Pickford (1956), it is regarded by Erspamer (1954) as a normal and important function of this substance in the body. Smith et al (1957) found that the kidney was in fact able to deal with the water load in four of their cases, the study of which led them to suggest that the antidiuretic effect of 5-H.T.…”

A Delayed Slow Contracting Effect of Serum and Plasma Due to the Release of a Substance Resembling Kallidin and Bradykinin

“…Hen serum contained large amounts (approximately 1.0 jug./ml.) ofa substance resembling 5-hydroxytryptamine (see Erspamer and Sala, 1954).…”

“…Human and cat serum did not produce effects as pronounced, or as regular after dilution, as did ox and guinea-pig serum; but an effect was usually detectable and was occasionally marked (cf., Fig. 4 Erspamer and Sala, 1954).…”