Somatostatin metabolism by the isolated rat lung.

We have previously reported that somatostatin-14 (S-14) and somatostatin-28 (S-28) are degraded by the rat liver. Since pulmonary enzymes known to degrade peptides such as angiotensin resemble hepatic somatostatin-degrading peptidases, the present studies were undertaken to investigate and characterize somatostatin metabolism by the lung. Isolated rat lungs were perfused in situ with synthetic S-14 or S-28. Degradation of the cyclic (ring) portion common to S-14 and S-28 was monitored by RIA as disappearance of S-14-like immunoreactivity, (S-14 LI) (ring-directed immunoreactivity). N-Terminal cleavage of S-28 was separately assessed by an RIA directed against S-28[1-14] (S-28[1-14]LI). In addition, S-28 perfusates were analyzed by gel chromatography and RIA (S-14 LI). Both S-14 and S-28 were significantly metabolized by the lung. The ring portion of S-28 was found to be degraded significantly more slowly (t 1/2 = 56.1 +/- 5.2 min) than the ring of S-14 (t 1/2 = 23.8 +/- 2.1 min) and the N-terminus of S-28 (t 1/2 = 32.2 +/- 3.0 min). S-14 was demonstrated to be a minor pulmonary metabolite of S-28. The lung was shown to release S-14 and S-28 ring-degrading enzymes into the perfusate. These data suggest that the lung is capable of metabolizing S-14 and S-28 by enzymatic mechanisms which are similar to those reported for the liver.