Regulation of cholecystokinin secretion by calcium-dependent calmodulin kinase II: differential effects of phenylalanine and cAMP.
The release of cholecystokinin was investigated in STC-1 cells, an intestinal cholecystokinin-secreting cell line. Fifteen minute incubation of cells with the amino acid, L-phenylalanine (20 mM), or the phosphodiesterase inhibitor, IBMX (100 microM), stimulated cholecystokinin secretion. Stimulation of secretion by both agents was associated with an increase in cytosolic calcium and was inhibited by the calcium channel blocker, diltiazem (10 microM). The calcium-calmodulin kinase II inhibitor, KN-65 (1.4 microM), markedly reduced IBMX-stimulated secretion, but had no effect on phenylalanine-mediated activity. KN-62 also inhibited IBMX-induced increases in cytosolic calcium, suggesting that cAMP may activate diltiazem-sensitive calcium channels by a calmodulin-dependent process.
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Department of Medicine, Duke University Medical Center, Durham, NC.
Basavappa
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Liddle
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Mangel
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D010649:Phenylalanine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects
D007546:Isoquinolines; D010879:Piperazines; D010649:Phenylalanine; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002766:Cholecystokinin; D000242:Cyclic AMP; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004110:Diltiazem; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine