Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2007154 | Peptides | 2008 | 8 Pages |
Abstract
Cultured rat cortical astrocytes express two types of urotensin II (UII) binding sites: a high affinity site corresponding to the UT (GPR14) receptor and a low affinity site that has not been fully characterized. Activation of the high affinity site in astroglial cells stimulates polyphosphoinositide (PIP) turnover and provokes an increase in intracellular calcium concentration. We have hypothesized that the existence of distinct affinity sites for UII in rat cortical astrocytes could be accounted for by a possible cross-talk between UT and the ligand-gated ion channel GABAA receptor (GABAAR). Exposure of cultured astrocytes to UII provoked a bell-shaped increase in cAMP production, with an EC50 stimulating value of 0.83 ± 0.04 pM, that was totally blocked in the presence of the adenylyl cyclase inhibitor SQ 22,536. In contrast, UII was found to inhibit forskolin-induced cAMP formation. In the presence of the specific PKA inhibitor H89, UII provoked a sustained stimulation of cAMP formation. Inhibition of PKA by H89 strongly reduced the stimulatory effect of UII on PIP metabolism. GABA and the GABAAR agonist isoguvacine provoked a marked inhibition of UII-induced cAMP synthesis and a significant reduction of UII-evoked PIP turnover. These data suggest that functional interaction between UT and GABAAR negatively regulates coupling of UT to the classical PLC/IP3 signaling cascade as well as to the adenylyl cyclase/PKA pathway.
Keywords
IBMXDMEMFBSPolyphosphoinositideHEPESGFAPgamma-aminobutyric acid type A receptorPKCpKaPLCPBSGPCRDulbecco's modified Eagle's mediumN-2-hydroxyethylpiperazine-N′-2-ethane sulfonic acid[Ca2+]cadenylyl cyclaseisobutylmethylxanthinefetal bovine serumcytosolic calcium concentrationPhosphate buffered salinephospholipase CGlial fibrillary acidic proteinprotein kinase AProtein kinase CPiPGABAARG protein-coupled receptor
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Authors
Laurence Desrues, Thomas Lefebvre, Mickaël Diallo, Pierrick Gandolfo, Jérôme Leprince, David Chatenet, Hubert Vaudry, Marie-Christine Tonon, Hélène Castel,