Crosstalk between Gαi- and Gαq-coupled receptors is mediated by Gβγ exchange

摘要: Activation of Gαi-coupled receptors often causes enhancement the inositol phosphate signal triggered by Gαq-coupled receptors. To investigate mechanism this synergistic receptor crosstalk, we studied adenosine A1 and α2C adrenergic bradykinin B2 a UTP-preferring P2Y receptor. Stimulation either expressed in COS cells increased potency efficacy production or UTP. Likewise, overexpression Gβ1γ2 resulted similar increase In contrast, these stimuli did not affect direct activators Gαq; truncated Gβ3 mutant had no effect on receptor-generated signals whereas generated at G-protein level were still enhanced. This suggests that Gβγ-mediated occurs level. Almost all possible combinations Gβ1–3 with Gγ2–7 equally effective enhancing receptor, indicating very broad specificity synergism. The (i) Gαi-activating ligands (ii) cotransfection Gβγ was suppressed when replaced B2Gβ2 fusion protein. enhanced receptor-stimulated activation G-proteins as determined GTPγS-induced decrease high affinity agonist binding receptor-enhanced [35S]GTPγS binding. These findings support concept exchange between Gαi- mediates type crosstalk.