Control of somatostatin (SS) secretion by CCK-1 and CCK-2 receptors' occupation in RIN-14B cells, a rat pancreatic islet cell line.
OBJECTIVE
This study evaluated the role played by cholecystokinin (CCK) receptors' occupation in the control of somatostatin (SS) secretion in RIN-14B cells.


METHODS
The presence of the CCK receptors 1 and 2 was confirmed by immunofluorescence, and SS secretion was evaluated by enzyme-linked immunosorbent assay.


RESULTS
By immunofluorescence, 95% of the cell population was composed of SS cells bearing both CCK-R subtypes with 5% of beta cells (data not shown). Cerulein (Cae), a CCK-1R agonist, and pentagastrin, a CCK-2R agonist, dose-dependently increased SS release, 3-fold at 1 mumol/L Cae, 2.5-fold at 10 mumol/L pentagastrin, with occupation of both CCKRs confirmed by L-364,178 and L-365,260 inhibition of CCK receptors 1 and 2. The occupation of high-affinity CCK-1R by Cae was confirmed on SS release with JMV-180, a high-affinity CCK-1R agonist, and absence of SS release inhibition at high Cae concentration occupying the low-affinity CCK-1R. These cells release more than 60% of their SS content by constitutive secretion, confirmed by cycloheximide and brefeldin inhibiting SS synthesis and intracellular trafficking, respectively.


CONCLUSIONS
Both CCKR subtypes occupy RIN-14B cells and initiate SS secretion through constitutive secretion controlled at SS synthesis level. Somatostatin secretion via the CCK-1R occupation mobilizes its high-affinity sites.
El-Kouhen
Karim
K
Faculty of Medicine, Department of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Morisset
Jean
J
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D002460:Cell Line; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D020109:Devazepide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005755:Gastrins / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D010418:Pentagastrin / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D051381:Rats; D043886:Receptor, Cholecystokinin A / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043887:Receptor, Cholecystokinin B / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013004:Somatostatin / Q000096:biosynthesis / Q000378:metabolism*
D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; D011498:Protein Precursors; D011500:Protein Synthesis Inhibitors; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; C058451:JMV 180; D020126:Brefeldin A; C058121:L 365260; C013706:big gastrin; D013004:Somatostatin; D002108:Ceruletide; D002766:Cholecystokinin; D003513:Cycloheximide; D010418:Pentagastrin; D020109:Devazepide; D012844:Sincalide