Evidence for the release of bradykinin in carcinoid syndrome.

In a previous report (2), it was shown that a kinin peptide was released into the hepatic venous blood of some patients with carcinoid syndrome during flushes induced by epinephrine. A kinin-forming enzyme (kallikrein) was found in several carcinoid tumors. The kinin obtained from the hepatic venous blood of these patients has been further examined in the present studies. The physicochemical characteristics, enzymatic inacti-vation, and pharmacologic properties of this substance indicate that it is bradykinin. Studies on the formation of this kinin are also reported. Methods Materials. Synthetic bradykinin1 and synthetic lysyl-bradykinin 2 were employed. Triple-crystallized salt free lyophilized trypsin and lyophilized chymotrypsin were purchased.3 IRC-50 (CG-50) 100 to 200 mesh, hydrogen form 4 was prepared as follows: The resin was washed twice with distilled water, washed repeatedly with 3 N ammonium hydroxide until the pH exceeded 9 (pH meter), washed with water, washed with 4 N acetic acid to reduce the pH below 3.5, washed again with water, titrated with 3 N ammonium hydroxide to the appropriate pH (5.4 or 6.0), washed with water, and stored with a 0.1 M ammonium acetate buffer of the same pH. Methods for purification and physicochemical characterization of the carcinoid kinin. In the previous study (2), increased amounts of a kinin peptide were found in the blood of patients with carcinoid syndrome during flushes induced with epinephrine. The present studies on the characterization of this kinin were carried out on the peptide found in hepatic venous blood samples from four of these patients (F. equivalent to 39 to 120 ,ug of bradykinin per 100 ml of blood were present in these samples. The blood was drawn rapidly from a catheter in the hepatic vein and immediately precipitated with ethanol, after which the kinin was separated by a cation exchange column procedure , as previously described (2). Five to 10%o of the eluates from these columns was used for assay of the kinin on the rat uterus and other procedures; the remainder was frozen until further purification was undertaken. Additional purification of this kinin was achieved by fractional elution from a weakly acidic cation exchange resin. The eluates from the initial column procedure were adjusted to pH 5.4. They were then passed over a 6-X 50-mm column of IRC-50 (NH, form). After the sample was applied, the column was washed with 20 ml 0.2 M ammonium phosphate, pH 6.6, followed by 5 ml H20. …