Studies on Urinary Excretion of Histamine in the Rat Part 2. Actions on the Urinary Excretion of Histamine, of the Histamine Releasers of Different Classes and of the Substances Affecting Histamine Release

With the administration of histamine there occurs a transient increase of the urinary excretion of free histamine in the female rat being loaded with water and whose urine being collected every 30 minutes. In the previous paper (Folia pharmacol. japon. 54, 1221, 1958) it was reported that such an increase is dependent upon the basal rate (a) of the urinary excretion of histamine and the amount (b) of histamine excessively excreted after intraperitoneal injection of a limited amount of histamine and that there is a relationship of b/a=k (k stands for constant pertaining dose). On the basis of these findings and taking the increase in the urinary excretion of histamine as an index, the author compared the potency and time course of in vivo histamine release as demonstrated by sinomenine hydrochloride, Compound 48/80, quinine hydrochoride, sodium cholate, dextran, egg white, decylamine and Tween 20, administered intraperitoneally. Judging from the relationship between the degree of the increase in the urinary excretion of histamine and the amount of the substances being administered, the histamine-releasing ability of these substances was found to be in the order of; Compound 48/80>decylamine>sinomenine>sodium cholate>quinine, Tween 20>dextran and egg white. Of them, Compound 48/80 and sinomenine showed the increase in the urinary histamine exactly identical with that observed after histamine administration, taking the shortest time course; while in the cases of quinine, sodium cholate, dextran, and egg white the increase was somewhat slower; and by decylamine and Tween 20 it developed most slowly yet most persistently. In the rats previously treated with guaiazulene, cortisone, aminopyrine or cinchophen sodium, increases in the urinary excretion of histamine by all the releasers mentioned above were similarly inhibited. Since mechanisms of histamine release action are not the same by different releasers, it seems that the action of these inhibitors is of such a nature as to be manifested at a common stage involved in different patterns of the mechanism of histamine release. Such an action of cortisone was more marked in a relatively small dose rather than in a large dose, suggesting presence of an adequate amount of this steroid to be used for the manifestation of this action. The histamine-releasing ability of egg white was inhibited in the alloxan-diabetic rat, while on the contrary, it was greatly accelerated in the insulin-treated rat. Such an effect of alloxan was completely antagonized by an adequate amount of insulin. However, in the rat with glycosuria induced by glucose administration, sensitivity to egg white was not altered. Succinic acid or oxaloacetic acid given with the purpose to inhibit the formation of keton bodies, could not eliminate the above mentioned alloxan effect. Both alloxan and insulin did not in any way modify the histamine-releasing effect of sinomenine.