Inhibition of phospholipase C-ε by Gi-coupled receptors
| Autor: | Harald Sanders, Melanie Keiper, Aysegül Y Sari, Paschal A. Oude Weernink, Karl Jakobs, Martina Schmidt, Frank vom Dorp |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Stimulation
Adenylyl cyclase chemistry.chemical_compound Phosphoinositide Phospholipase C Sphingosine Receptors Opioid delta Muscarinic acetylcholine receptor Cyclic AMP Guanine Nucleotide Exchange Factors Humans Enzyme Inhibitors Receptor Cells Cultured G protein-coupled receptor Forskolin Phospholipase C Colforsin ADCY9 Cell Biology Receptors Muscarinic Molecular biology rap GTP-Binding Proteins Pertussis Toxin chemistry Type C Phospholipases Lysophospholipids Signal Transduction |
| Zdroj: | Cellular Signalling. 16:921-928 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2004.01.009 |
| Popis: | We recently reported that several G s -coupled receptors stimulate phospholipase C (PLC)-e via increased formation of cyclic AMP and subsequent activation of the small GTPase Rap2B by the cyclic AMP-activated exchange factor Epac1. Here we show by studies in HEK-293 and N1E-115 neuroblastoma cells that this stimulation induced by G s -coupled receptors or the direct adenylyl cyclase activator, forskolin, is potently inhibited by G i -coupled receptors, known to inhibit cyclic AMP formation. PLC inhibition by the overexpressed M 2 muscarinic receptor and the endogenously expressed sphingosine-1-phosphate and δ-opioid receptors was fully pertussis toxin-sensitive and accompanied by a reduction in Rap2B activation induced by G s -coupled receptors. In contrast, Rap2B activation and PLC stimulation induced by membrane-permeable cyclic AMP analogues, including an Epac-specific activator, or PLC stimulation caused by constitutively active Rap2B were not affected by the G i -coupled receptors. In summary, our data indicate that G i -coupled receptors can inhibit PLC-e, most likely by suppressing formation of cyclic AMP required for Epac-mediated Rap2B activation. |
| Databáze: | OpenAIRE |
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