Presence of an Antagonistic Factor in Serum of Dogs Following Repeated Injections of Cortin. ∗

Abstract

It has been reported 1 that in the normal dog a marked decrease in the excretion of Na and usually an increase in the excretion of K occurs during a 6-hour period following the intravenous injection of 20-40 cat units of cortin; and that with repeated injections (at intervals of several days), the effect becomes progressively less, until there is little change in electrolyte excretion following administration of the extract. It has since been found that NH₃ excretion is also increased following cortin and that with repeated injections this response is decreased. Of 9 animals injected with 20-40 cat units of cortin, all gave the characteristic electrolyte response described (Table I). Four different cortical extracts prepared in this laboratory were used. The response elicited by a given extract in different dogs was very similar (Table I). Five of these animals were injected until they became completely refractory.

Failure of these animals to respond to further injections suggested the possibility that some antagonistic substance was present in the blood. Using sterile precautions, blood was taken from 2 dogs (I and 111), which had received 7 and 11 injections respectively over periods of 5 and 9 weeks. The serum was separated and stored at 4°C. Five untreated animals were given 10-25 cc. of this serum intravenously about 15 minutes previous to the injection of the usual amount of cortin. In every case in which cortin and serum were given, the Na and the NH, did not change beyond the range of the controls, whereas cortin alone always reduced the Na to a level well below that of the lowest control and increased the NH, well above the highest control value (Table 11). Decreases in Na of 86-890/, in 3 animals (I, 111, X) were shown when 0.5 cc.