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| Content Provider | PubMed Central |
|---|---|
| Author | Ursula, Quitterer Lohse, Martin J. |
| Copyright Year | 1999 |
| Abstract | Activation of Gαi-coupled receptors often causes enhancement of the inositol phosphate signal triggered by Gαq-coupled receptors. To investigate the mechanism of this synergistic receptor crosstalk, we studied the Gαi-coupled adenosine A1 and α2C adrenergic receptors and the Gαq-coupled bradykinin B2 and a UTP-preferring P2Y receptor. Stimulation of either Gαi-coupled receptor expressed in COS cells increased the potency and the efficacy of inositol phosphate production by bradykinin or UTP. Likewise, overexpression of Gβ1γ2 resulted in a similar increase in potency and efficacy of bradykinin or UTP. In contrast, these stimuli did not affect the potency of direct activators of Gαq; a truncated Gβ3 mutant had no effect on the receptor-generated signals whereas signals generated at the G-protein level were still enhanced. This suggests that the Gβγ-mediated signal enhancement occurs at the receptor level. Almost all possible combinations of Gβ1–3 with Gγ2–7 were equally effective in enhancing the signals of the B2 and a UTP-preferring P2Y receptor, indicating a very broad specificity of this synergism. The enhancement of the bradykinin signal by (i) Gαi-activating receptor ligands or (ii) cotransfection of Gβγ was suppressed when the B2 receptor was replaced by a B2Gβ2 fusion protein. Gβγ enhanced the B2 receptor-stimulated activation of G-proteins as determined by GTPγS-induced decrease in high affinity agonist binding and by B2 receptor-enhanced [35S]GTPγS binding. These findings support the concept that Gβγ exchange between Gαi- and Gαq-coupled receptors mediates this type of receptor crosstalk. |
| Starting Page | 10626 |
| File Format | |
| ISSN | 10916490 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 19 |
| Volume Number | 96 |
| Language | English |
| Publisher | The National Academy of Sciences |
| Publisher Date | 1999-09-14 |
| Access Restriction | Open |
| Rights Holder | The National Academy of Sciences |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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