title: Inhibitory effect of gastrin and cholecystokinin fragments on the secretion of triacylglycerol in rat hepatocytes.
abstract: In this investigation we studied the influence of two gastrin fragments, pentagastrin and nonsulfated heptadecagastrin, and two cholecystokinin fragments, sulfated and desulfated cholecystokinin 26-33, on intracellular and secreted triacylglycerol in isolated hepatocyte cultures. Both gastrin fragments inhibited triacylglycerol release in a biphasic manner, exhibiting maximal effect at 0.1 nmol/L (nonsulfated heptadecagastrin) and 0.3 nmol/L (pentagastrin). At these concentrations triacylglycerol secretion was 42% (nonsulfated heptadecagastrin, p < 0.001) and 62% (pentagastrin, p < 0.001) lower than in cells untreated with gastrin. Sulfated cholecystokinin 26-33 caused a 35% decrease in triacylglycerol secretion at 0.1 nmol/L (p < 0.01), and desulfated cholecystokinin 26-33 caused a 53% decrease at 0.2 nmol/L (p < 0.001). In all experiments, the hormone-induced decrease in triacylglycerol secretion was accompanied by an increase in intracellular triacylglycerol content. The cholecystokinin-A receptor antagonist L-364, 718 did not affect the decrease in triacylglycerol secretion induced by 0.3 nmol/L pentagastrin, whereas the cholecystokinin-B receptor antagonist L-365, 260 inhibited the pentagastrin effect at concentrations above 50 nmol/L. These results suggest that gastrin, cholecystokinin or some other gastrinlike hormone (or all three) may play a previously unrecognized regulatory role with respect to hepatic very low density lipoprotein secretion.
authors.affiliation: Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lindholm
authors.forename: A
authors.initials: A
authors.lastname: Eklund
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002478:Cells, Cultured; D003864:Depression, Chemical; D020109:Devazepide; D005755:Gastrins / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010671:Phenylurea Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D001570:Benzodiazepinones; D005755:Gastrins; D010446:Peptide Fragments; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D014280:Triglycerides; C058121:L 365260; C013550:gastrin 17; C044201:cholecystokinin (26-33); D010418:Pentagastrin; D020109:Devazepide; D012844:Sincalide