Dopamine D1 and D2 Receptor Co-activation Generates a Novel Phospholipase C-mediated Calcium Signal Export

@article{citeulike:3929038, abstract = {Although dopamine D1 and D2 receptors belong to distinct subfamilies of dopamine receptors, several lines of evidence indicate that they are functionally linked. However, a mechanism for this linkage has not been elucidated. In this study, we demonstrate that agonist stimulation of co-expressed D1 and D2 receptors resulted in an increase of intracellular calcium levels via a signaling pathway not activated by either receptor alone or when only one of the co-expressed receptors was activated by a selective agonist. Calcium signaling by D1-D2 receptor co-activation was abolished following treatment with a phospholipase C inhibitor but not with pertussis toxin or inhibitors of protein kinase A or protein kinase C, indicating coupling to the Gq pathway. We also show, by co-immunoprecipitation from rat brain and from cells co-expressing the receptors, that D1 and D2 receptors are part of the same heteromeric protein complex and, by immunohistochemistry, that these receptors are co-expressed and co-localized within neurons of human and rat brain. This demonstration that D1 and D2 receptors have a novel cellular function when co-activated in the same cell represents a significant step toward elucidating the mechanism of the functional link observed between these two receptors in brain. 10.1074/jbc.M401923200}, author = {Lee, Samuel P. and So, Christopher H. and Rashid, Asim J. and Varghese, George and Cheng, Regina and Lanca, A. Jose and O'Dowd, Brian F. and George, Susan R.}, citeulike-article-id = {3929038}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M401923200}, citeulike-linkout-1 = {http://stke.sciencemag.org/content/jbc;279/34/35671.abstract}, citeulike-linkout-2 = {http://stke.sciencemag.org/content/jbc;279/34/35671.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/15159403}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=15159403}, day = {20}, doi = {10.1074/jbc.M401923200}, issn = {0021-9258}, journal = {J. Biol. Chem.}, keywords = {d1, d2, heteromers, kenntnisstandprufung}, month = {August}, number = {34}, pages = {35671--35678}, posted-at = {2009-01-23 12:54:47}, priority = {2}, title = {Dopamine D1 and D2 Receptor Co-activation Generates a Novel Phospholipase C-mediated Calcium Signal}, url = {http://dx.doi.org/10.1074/jbc.M401923200}, volume = {279}, year = {2004} }

TY - JOUR ID - citeulike:3929038 L3 - citeulike-article-id:3929038 N2 - Although dopamine D1 and D2 receptors belong to distinct subfamilies of dopamine receptors, several lines of evidence indicate that they are functionally linked. However, a mechanism for this linkage has not been elucidated. In this study, we demonstrate that agonist stimulation of co-expressed D1 and D2 receptors resulted in an increase of intracellular calcium levels via a signaling pathway not activated by either receptor alone or when only one of the co-expressed receptors was activated by a selective agonist. Calcium signaling by D1-D2 receptor co-activation was abolished following treatment with a phospholipase C inhibitor but not with pertussis toxin or inhibitors of protein kinase A or protein kinase C, indicating coupling to the Gq pathway. We also show, by co-immunoprecipitation from rat brain and from cells co-expressing the receptors, that D1 and D2 receptors are part of the same heteromeric protein complex and, by immunohistochemistry, that these receptors are co-expressed and co-localized within neurons of human and rat brain. This demonstration that D1 and D2 receptors have a novel cellular function when co-activated in the same cell represents a significant step toward elucidating the mechanism of the functional link observed between these two receptors in brain. 10.1074/jbc.M401923200 IS - 34 JF - J. Biol. Chem. SN - 0021-9258 EP - 35678 TI - Dopamine D1 and D2 Receptor Co-activation Generates a Novel Phospholipase C-mediated Calcium Signal VL - 279 SP - 35671 KW - d1 KW - d2 KW - heteromers KW - kenntnisstandprufung AU - Lee, Samuel AU - So, Christopher AU - Rashid, Asim AU - Varghese, George AU - Cheng, Regina AU - Lanca, Jose AU - O'Dowd, Brian AU - George, Susan PY - 2004/08/20/ UR - http://dx.doi.org/10.1074/jbc.M401923200 ER -