Inhibitory effect of gastrin and cholecystokinin fragments on the secretion of triacylglycerol in rat hepatocytes.
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.
Lindholm
M
M
Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.
Eklund
A
A
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*
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