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 fragment s, pentagastrin and nonsulfated heptadecagastrin, and two cholecystoki nin fragments, sulfated and desulfated cholecystokinin 26-33, on intra cellular and secreted triacylglycerol in isolated hepatocyte cultures. Both gastrin fragments inhibited triacylglycerol release in a biphasi c manner, exhibiting maximal effect at 0.1 nmol/L (nonsulfated heptade cagastrin) and 0.3 nmol/L (pentagastrin). At these concentrations tria cylglycerol secretion was 42% (non-sulfated heptadecagastrin, p < 0.00 1) and 62% (pentagastrin, p < 0.001) lower than in cells untreated wit h gastrin. Sulfated cholecystokinin 26-33 caused a 35% decrease in tri acylglycerol secretion at 0.1 nmol/L (p < 0.01), and desulfated cholec ystokinin 26-33 caused a 53% decrease at 0.2 nmol/L (p < 0.001). In al l experiments, the hormone-induced decrease in triacylglycerol secreti on was accompanied by an increase in intracellular triacylglycerol con tent. The cholecystokinin-A receptor antagonist L-364, 718 did not aff ect the decrease in triacylglycerol secretion induced by 0.3 nmol/L pe ntagastrin, whereas the cholecystokinin-B receptor antagonist L-365, 2 60 inhibited the pentagastrin effect at concentrations above 50 nmol/L . These results suggest that gastrin, cholecystokinin or some other ga strinlike hormone (or all three) may play a previously unrecognized re gulatory role with respect to hepatic very low density lipoprotein sec retion.