Studies on an Antidiuretic Substance in the Bile -Report Ⅲ. Origin of the biliary antidiuretic substance-

(Ｉ）Relationship between the biliary ADS and vasopressin 1) Intravenously injected Pitressin (vasopressin) was excreted into the bile, suggesting that the biliary ADS may be derived from vasopressin. 2) In contrast to Pitressin, the biliary ADS caused neither elevation of blood pressure in normal cats and rabbits nor increase in urinary concentration of Na, Cl and K ions in bilaterally adrenalectomized rats. However, this does not necessarily mean that the biliary ADS is entirely different from Pitressin, since Pitressin loses these activities without losing the antidiuretic actiivity, when subjected to the same procedure employed for extraction of the biliary ADS. 3) The biliary ADS as well as Pitressin showed an anti-epinephrinic action when tested by mesoappendic test. 4) Potency of the biliary ADS in a case of diabetes insipidus ranged within normal linits. If the blilary ADS were derived from vasopressin, the antidiuretic potency of the bile of such a patient should be diminished, because the etiology of this disease involves a lack of vasopressin excretion. The results proved to be otherwise. Nevertheless, this does not necessarily indicate that biliary ADS is not derived from vasopressin, because of the limited observation. Furthermore, the urine of the patient had an antidiuretic activity. The potencies of both biliary and urinary ADS were increased in this case after a treatment with vasopressin. 5) The biliary ADS as well as Pitressin was found to be considerably resistant to heating in an acid medium(Ph 3), but they were readily inactivated by incubation for 2 hours at room temperature in an alkaline medium(Ph 13). 6) In hypophysectomized rats, as in normal rats, an injection of the biliary ADS showed an antidiuretic and anti-epnephrinic action as tested by mesoappendic test. Thus, the biliary ADS acts directly on the kidney or meesoappendic vessels. Because of the fact that ferritin exerts its antidiuretic action through the pituitary gland, it might be reasonable to assume that the biliary ADS is similar to vasopressin rather than to ferritin. However, this is far from a conclusion, because unidentity of the biliary ADS with ferritin is as yet established. (Ⅱ) Studies on the oridin of the biliary ADS 7)When the perfusion experiments were carried out with rabbit livers whose function was accelerated by an injection of sodium hippurate, a hepatotonica, or by maintaining the animal under an anuric condition for 24 hours by bilateral nephrectomy, no new antidiuretic sucstance was appeared in the perfusate upon prolonged perfusion. The production of the new antidiuretic substance in the perfusate was accompanied by an increase of the antidiuretic substance and ferritin in the liver tissue. These facts suggest that the antidiuretic substance in the perfusate may have some relation to hepatic exhaustion. 8) The antidiuretic activity of the bile was more potent in patients with liver disazses than in normals. The activity in cases of acute hepatitis returned to the normal range with liver diseases was equal to or greater than that of the normal subjects. However, no correlation was obtained between the potency of the biliary ADS and that of the urinary ADS.