The metabolism of gastrin-52 and gastrin-6 in pigs.
The kinetics and metabolism in various organs of three bioactive products of progastrin, the small sulfated and nonsulfated gastrin-6 and the large nonsulfated gastrin-52, were examined during intravenous administration in anesthetized pigs. The kidney, hindlimb, liver, head, and gut eliminated the hexapeptides efficiently, with a fractional extraction ranging from 0.50 to 0.28 (P<0.001-0.05). No metabolism was recorded in the lungs, and sulfation was without influence on the extraction of gastrin-6. Gastrin-52 was eliminated only in the kidney and the head, with a fractional extraction between 0.23 and 0.11 (P<0.01-0.05). The half-life of sulfated and nonsulfated gastrin-6 was 1.5+/-0.4 and 1.4+/-0.3 min, the metabolic clearance rate (MCR) was 80.8+/-7.6 and 116.0+/-13.5 ml x kg(-1) x min(-1) (P<0.05), and the apparent volume of distribution (V(dss)) was 199.3+/-70.1 and 231.4+/-37.3 ml/kg, respectively. The decay of gastrin-52 in plasma was biexponential. The half-lives of this biexponential after a bolus injection were 3.9+/-0.5 (T(1/2alpha)) and 25.7+/-1.4 (T(1/2beta)) min, and the MCR and V(dss) were 4.2+/-0.4 ml. kg(-1) x min(-1) and 116.2+/-16.2 ml/kg(1). We conclude that there is a differential elimination of progastrin products in splanchnic and nonsplanchnic tissue, which depends on the chain length of the peptides. Sulfation of gastrin-6 had no influence on the organ-specific extraction but reduced the MCR. Our results are in keeping with previous studies of nonsulfated gastrin-17, which is extracted in the kidney, head, limb, and gut but not in the liver.
Hansen
C P
CP
Department of Gastrointestinal Surgery and Clinical Biochemistry, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Goetze
J P
JP
Stadil
F
F
Rehfeld
J F
JF
D000758:Anesthesia; D000818:Animals; D002850:Chromatography, Gel; D005755:Gastrins / Q000097:blood / Q000493:pharmacokinetics*; D006439:Hemodynamics / Q000502:physiology; D006728:Hormones / Q000097:blood / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000493:pharmacokinetics*; D011168:Portal System / Q000502:physiology; D011498:Protein Precursors / Q000097:blood / Q000493:pharmacokinetics*; D011863:Radioimmunoassay; D013431:Sulfates / Q000097:blood / Q000493:pharmacokinetics; D013552:Swine
D005755:Gastrins; D006728:Hormones; D010446:Peptide Fragments; D011498:Protein Precursors; D013431:Sulfates; C013706:big gastrin; C013550:gastrin 17