The hepatic clearances of somatostatin (SS)-28 and SS-14 by the perfused rat liver were compared, using a recirculating, plasma-free, erythrocyte-containing perfusion system. The disappearance rate constant, half time, clearance, and hepatic extraction ratio when 1.2 nM SS-28 was added to the perfusate were 0.0221 ± 0.0051 min−1, 36.6 ± 7.6 min, 0.34 ± 0.08 mL/min, and 17.2 ± 3.9%, respectively. The corresponding values obtained when SS-14 was added to the perfusate were 0.0405 ± 0.0022 min−1, 17.3 ± 1.0 min, 0.71 ± 0.05 mL/min, and 35.4 ± 2.6%, respectively. The differences between the SS-28 and SS-14 indices were all statistically significant. In addition, the perfusates with SS-28 added were eluted on Sephadex G-25 fine columns and somatostatinlike immunoreactivity (SLI) was determined. No SS-14 was found in perfusate containing SS-28 at both 5 and 30 min after the beginning of the perfusion. To investigate whether or not the liver plays an important role in the clearance of SS-28 or the conversion of SS-28 to SS-14 in vivo, the plasma disappearance of 2 μg SS-28 was compared in the whole rat and the functionally hepatectomized model. The half time of plasma SS-28 was 1.43 ± 0.12 min in the whole rat, significantly shorter than the 2.20 ± 0.14 min in the hepatectomized model. Gel filtration of plasma extract samples at 0.5 min after the SS-28 injection showed two major peaks of SLI: a first peak corresponding to SS-28 and a second peak coeluted in the position of SS-14 in both the whole rat and the hepatectomized model. At 4 min after the SS-28 injection, the first peak disappeared and only a small second peak was observed. These results suggest that SS-28 is cleared by the rat liver in vivo and in vitro and that it is cleared more slowly than SS-14. Furthermore, we find that little, if any, conversion of SS-28 to SS-14 occurs in the liver.
Regulation of phenylalanine hydroxylase activity by phenylalanine in vivo, in vitro, and in perfused rat liver.
