%0 Journal Article %1 Quitterer1999 %A Quitterer, U. %A Lohse, M. J. %D 1999 %J Proc Natl Acad Sci U S A %K Animals B2 Biological Bradykinin Bradykinin/*metabolism C COS Calcium/metabolism Cross-Talk/*physiology Dose-Response Drug Factors Fusion GTP-Binding Immunoblotting Inositol Models, Mutagenesis Phosphates/metabolism Phospholipases/metabolism Proteins/metabolism Receptor Recombinant Relationship, Signal Time Transduction Transfection Triphosphate/metabolism Type Uridine beta-2/metabolism Cell Adrenergic %N 19 %P 10626-31 %T Crosstalk between Galpha(i)- and Galpha(q)-coupled receptors is mediated by Gbetagamma exchange %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10485876 %V 96 %X Activation of Galpha(i)-coupled receptors often causes enhancement of the inositol phosphate signal triggered by Galpha(q)-coupled receptors. To investigate the mechanism of this synergistic receptor crosstalk, we studied the Galpha(i)-coupled adenosine A(1) and alpha(2C) adrenergic receptors and the Galpha(q)-coupled bradykinin B(2) and a UTP-preferring P2Y receptor. Stimulation of either Galpha(i)-coupled receptor expressed in COS cells increased the potency and the efficacy of inositol phosphate production by bradykinin or UTP. Likewise, overexpression of Gbeta(1)gamma(2) 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 Galpha(q); a truncated Gbeta(3) mutant had no effect on the receptor-generated signals whereas signals generated at the G-protein level were still enhanced. This suggests that the Gbetagamma-mediated signal enhancement occurs at the receptor level. Almost all possible combinations of Gbeta(1-3) with Ggamma(2-7) were equally effective in enhancing the signals of the B(2) and a UTP-preferring P2Y receptor, indicating a very broad specificity of this synergism. The enhancement of the bradykinin signal by (i) Galpha(i)-activating receptor ligands or (ii) cotransfection of Gbetagamma was suppressed when the B(2) receptor was replaced by a B(2)Gbeta(2) fusion protein. Gbetagamma enhanced the B(2) receptor-stimulated activation of G-proteins as determined by GTPgammaS-induced decrease in high affinity agonist binding and by B(2) receptor-enhanced (35)SGTPgammaS binding. These findings support the concept that Gbetagamma exchange between Galpha(i)- and Galpha(q)-coupled receptors mediates this type of receptor crosstalk.

@article{Quitterer1999, abstract = {Activation of Galpha(i)-coupled receptors often causes enhancement of the inositol phosphate signal triggered by Galpha(q)-coupled receptors. To investigate the mechanism of this synergistic receptor crosstalk, we studied the Galpha(i)-coupled adenosine A(1) and alpha(2C) adrenergic receptors and the Galpha(q)-coupled bradykinin B(2) and a UTP-preferring P2Y receptor. Stimulation of either Galpha(i)-coupled receptor expressed in COS cells increased the potency and the efficacy of inositol phosphate production by bradykinin or UTP. Likewise, overexpression of Gbeta(1)gamma(2) 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 Galpha(q); a truncated Gbeta(3) mutant had no effect on the receptor-generated signals whereas signals generated at the G-protein level were still enhanced. This suggests that the Gbetagamma-mediated signal enhancement occurs at the receptor level. Almost all possible combinations of Gbeta(1-3) with Ggamma(2-7) were equally effective in enhancing the signals of the B(2) and a UTP-preferring P2Y receptor, indicating a very broad specificity of this synergism. The enhancement of the bradykinin signal by (i) Galpha(i)-activating receptor ligands or (ii) cotransfection of Gbetagamma was suppressed when the B(2) receptor was replaced by a B(2)Gbeta(2) fusion protein. Gbetagamma enhanced the B(2) receptor-stimulated activation of G-proteins as determined by GTPgammaS-induced decrease in high affinity agonist binding and by B(2) receptor-enhanced [(35)S]GTPgammaS binding. These findings support the concept that Gbetagamma exchange between Galpha(i)- and Galpha(q)-coupled receptors mediates this type of receptor crosstalk.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Quitterer, U. and Lohse, M. J.}, biburl = {https://www.bibsonomy.org/bibtex/25e1cb306b6619de6f426960ca1140842/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {4d830b578416e23820a79bf400ef9a28}, intrahash = {5e1cb306b6619de6f426960ca1140842}, issn = {0027-8424 (Print) 0027-8424 (Linking)}, journal = {Proc Natl Acad Sci U S A}, keywords = {Animals B2 Biological Bradykinin Bradykinin/*metabolism C COS Calcium/metabolism Cross-Talk/*physiology Dose-Response Drug Factors Fusion GTP-Binding Immunoblotting Inositol Models, Mutagenesis Phosphates/metabolism Phospholipases/metabolism Proteins/metabolism Receptor Recombinant Relationship, Signal Time Transduction Transfection Triphosphate/metabolism Type Uridine beta-2/metabolism Cell Adrenergic}, month = {Sep 14}, note = {Quitterer, U Lohse, M J United states Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10626-31.}, number = 19, pages = {10626-31}, shorttitle = {Crosstalk between Galpha(i)- and Galpha(q)-coupled receptors is mediated by Gbetagamma exchange}, timestamp = {2010-12-14T18:22:42.000+0100}, title = {Crosstalk between Galpha(i)- and Galpha(q)-coupled receptors is mediated by Gbetagamma exchange}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10485876}, volume = 96, year = 1999 }