Hepatic metabolism of neurotensin.
Neurotensin is released from the intestinal mucosa into the portal circulation and, to exert a systemic effect, it must traverse the liver intact. We examined the potential role of the liver in neurotensin clearance using the isolated perfused rat liver model. With N-terminal and C-terminal directed RIAs and HPLC, we demonstrated rapid metabolism of intact neurotensin to inactive N-terminal fragments in the isolated rat liver system. The disappearance half-lives of C-terminal and N-terminal immunoreactivity were 20.4 +/- 6.0 min and 82.7 +/- 7.7 min, respectively, (P less than 0.002). To assess whether this neurotensin disappearance might be due to metabolism within the perfusate itself by a peptidase released from liver, we further incubated neurotensin in perfusate previously circulated through liver. A rapid and progressive breakdown of intact neurotensin to N-terminal fragments was again shown. These data demonstrate that a substantial proportion of the hepatic clearance of neurotensin is attributable to release of a peptidase by the liver into the circulation.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D010446:Peptide Fragments; D009496:Neurotensin; D010447:Peptide Hydrolases