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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cervia, Davide Bouhelal, Rochdi Hoyer, Daniel Tenaillon, Laurent Nunn, Caroline Langenegger, Daniel |
| Description | Author Affiliation: Nunn C ( Neuroscience Research, Novartis Institutes for Biomedical Research, Novartis Pharma AG, CH-4002, Basel, Switzerland.) |
| Abstract | 1. Somatostatin (somatotropin release inhibiting factor; SRIF) acts via five G protein-coupled receptors (sst(1)-sst(5)) that modulate multiple cellular effectors. The aim of this study was to compare two functional effects of the human sst(2) receptor stably expressed in CHO-K1 cells in a single experiment using a duplex assay for intracellular calcium and serum response element (SRE)-driven luciferase expression. 2. Intracellular calcium was measured using a fluorometric imaging plate reader II (FLIPR II). SRIF-14 rapidly and transiently increased intracellular calcium with a pEC(50) of 8.74+/-0.03 (n=52). At 5 h after FLIPR II measurements, luciferase expression was determined. SRIF-14 concentration-dependently increased luciferase expression (pEC(50)=9.06+/-0.03, n=52). 3. Natural and synthetic agonist/antagonist ligands for SRIF receptors were tested in the duplex assay. Correlation of agonist potencies and efficacies between the two responses were significant (r(2)=0.83 and 0.90, pEC(50) and E(max), respectively). 4. Pertussis toxin pretreatment reduced SRIF-14/octreotide-mediated intracellular calcium increases by 45-47% and luciferase expression by 95-98%. 5. Thapsigargin pretreatment abolished the SRIF-14/octreotide-mediated intracellular calcium increase but had no effect on luciferase expression. 6. In conclusion, SRIF stimulates an increase in intracellular calcium and SRE-luciferase expression via human sst(2) receptors in CHO-K1 cells. The increase in luciferase is mediated via G(i)/G(o) while intracellular calcium increase is mediated by both G(i)/G(o) proteins and pertussis toxin-insensitive G proteins, and is mainly via release of calcium from intracellular stores. SRIF ligands display a similar recognition profile suggesting that the ligand/receptor/G protein/effector interaction is similar for the two parameters. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 142 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2004-05-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Calcium Metabolism Intracellular Fluid Luciferases Biosynthesis Receptors, Somatostatin Physiology Animals CHO Cells Cricetinae Dose-Response Relationship, Drug Gene Expression Regulation Drug Effects Genetics Protein Isoforms Agonists Somatostatin Pharmacology Comparative Study Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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