Plasma cholecystokinin and its precursors in hepatic cirrhosis.
OBJECTIVE
The liver influences the metabolism of several peptide hormones. The metabolic effect may, however, change considerably by diseases in the liver. This study examined whether hepatic cirrhosis influences the occurrence and concentrations of procholecystokinin (proCCK) and its products in plasma.


METHODS
The sum of proCCK and its products (both processing intermediates and bioactive fragments) in plasma were measured by a recently developed "processing-independent analysis". Bioactive forms of CCK in plasma were measured using a highly specific radioimmunoassay directed against the C-terminal epitope of CCK.


RESULTS
In plasma from patients with primary biliary cirrhosis the basal concentration of the total proCCK product was increased. Moreover, a mixed meal increased plasma concentrations of both bioactive CCK (i.e. carboxyamidated an 0-sulfated CCK peptides) and the total proCCK product in primary biliary cirrhosis. In contrast, plasma concentrations of bioactive CCK and the total proCCK product were normal in patients with alcoholic liver cirrhosis-both pre- or postprandially. The fraction of bioactive CCK in plasma from patients with both biliary and alcoholic cirrhosis was also normal. Hence, in primary biliary cirrhosis, alcoholic cirrhosis and in controls, respectively, bioactive CCK constituted 15%, 15% and 17% of the total proCCK product in the basal state; 70%, 58% and 53% 30 min after and 48%, 56% and 51% 90 min after the meal. As shown by gel chromatography, plasma from patients with primary biliary cirrhosis and controls sampled 30 min after a meal contained CCK-33, -22 and -8-like peptides. In addition, plasma contained non-amidated (approximately non-bioactive) proCCK products corresponding in size to CCK-83, -58 and -33. Ninety minutes after a meal, CCK-8 predominated in plasma from patients with primary biliary cirrhosis, whereas plasma from controls displayed a CCK profile similar to that obtained 30 min post-prandially.


CONCLUSIONS
The results show that CCK-8 is metabolized at a slower rate in patients with primary biliary cirrhosis.
Paloheimo
L I
LI
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark.
Clemmesen
O
O
Dalhoff
K
K
Rehfeld
J F
JF
D000328:Adult; D000577:Amides / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D002850:Chromatography, Gel; D000939:Epitopes; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood; D008105:Liver Cirrhosis, Biliary / Q000097:blood; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood*; D011863:Radioimmunoassay; D012016:Reference Values
D000577:Amides; D000939:Epitopes; D011498:Protein Precursors; C060249:procholecystokinin; D002766:Cholecystokinin