Effect of lanthanum on pancreatic protein synthesis in streptozotocin-diabetic rats.
The role of extracellular Ca2+ in mediating the stimulatory effect of cholecystokinin octapeptide (CCK8) on [3H]phenylalanine incorporation into protein was studied in isolated pancreatic acini from streptozotocin-diabetic rats. The stimulatory effect of CCK8 (10(-10) M) on [3H]phenylalanine incorporation was completely abolished by preincubating acini with either 10(-4) M lanthanum or 10(-3) M manganese. At these concentrations neither compound altered the basal rate of amino acid incorporation, and both compounds inhibited CCK-mediated Ca2+ influx without affecting either basal or CCK-mediated 45Ca2+ efflux. Lanthanum (10(-4) M) also blocked the stimulatory effect of the cholinergic analogue carbachol (10(-5) M) on amino acid incorporation but did not alter the stimulatory effect of insulin (1.67 x 10(-8) M). Vasoactive intestinal polypeptide and 12-O-tetradecanoyl-phorbol-13-acetate failed to increase the incorporation of [3H]phenylalanine into acinar protein. These findings suggest that CCK and other pancreatic secretagogues that act via Ca2+ enhance protein synthesis by increasing cell membrane permeability to Ca2+ and provide additional evidence that this may be an important mechanism by which CCK regulates pancreatic exocrine function.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D003515:Cycloleucine / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010649:Phenylalanine / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide
D007328:Insulin; D010446:Peptide Fragments; D003515:Cycloleucine; D008345:Manganese; D010649:Phenylalanine; D007811:Lanthanum; D002217:Carbachol; D002766:Cholecystokinin; D012844:Sincalide; D002118:Calcium