Transcription mediated by a cAMP-responsive promoter element is reduced upon activation of dopamine D2 receptors. Export

@article{citeulike:3037701, abstract = {Dopaminergic D2 receptors mediate the effect of dopamine on cellular effector systems by means of guanine nucleotide-binding proteins (G proteins). The major biochemical effect evoked by these receptors is the inhibition of adenylyl cyclase. As a consequence, the activation of D2 receptors lowers the intracellular cAMP level. Two cDNAs, originated by alternative splicing of the same gene, have been isolated: D2A and D2B. They code for two proteins of 444 and 415 amino acids. These proteins display high affinity for selective D2 dopamine ligands. D2A differs from D2B by an insertion of 87 nucleotides in its cDNA, which is located in a region of the protein considered important for the coupling to G proteins. To investigate functional differences between the two dopamine D2 receptor isoforms, we transiently expressed them in cultured cells. To do so we developed an assay to study membrane receptors that are coupled to the adenylyl cyclase. Using this assay, we were able to show that the stimulation of the adenylyl cyclase induced by the activation of the beta 2-adrenergic receptor is inhibited more efficiently by D2B than D2A. The effects elicited by the D2 receptors are mediated by pertussis toxin-sensitive G proteins. Treatment of transfected cells with pertussis toxin abolishes the inhibitory effects in a dose- and receptor isoform-dependent manner. Our results suggest that the two dopamine receptor isoforms are differentially coupled to G proteins.}, address = {Laboratoire de G\'{e}n\'{e}tique Mol\'{e}culaire des Eucaryotes, Institut National de la Sant\'{e} et de la Recherche M\'{e}dicale, Facult\'{e} de M\'{e}decine, Strasbourg, France.}, author = {Montmayeur, J. P. and Borrelli, E.}, citeulike-article-id = {3037701}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/1849644}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=1849644}, day = {15}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {camp, d2, dopamine, promoter, transcription}, month = {April}, number = {8}, pages = {3135--3139}, posted-at = {2008-07-23 21:32:01}, priority = {2}, title = {Transcription mediated by a cAMP-responsive promoter element is reduced upon activation of dopamine D2 receptors.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/1849644}, volume = {88}, year = {1991} }

TY - JOUR ID - citeulike:3037701 L3 - citeulike-article-id:3037701 N2 - Dopaminergic D2 receptors mediate the effect of dopamine on cellular effector systems by means of guanine nucleotide-binding proteins (G proteins). The major biochemical effect evoked by these receptors is the inhibition of adenylyl cyclase. As a consequence, the activation of D2 receptors lowers the intracellular cAMP level. Two cDNAs, originated by alternative splicing of the same gene, have been isolated: D2A and D2B. They code for two proteins of 444 and 415 amino acids. These proteins display high affinity for selective D2 dopamine ligands. D2A differs from D2B by an insertion of 87 nucleotides in its cDNA, which is located in a region of the protein considered important for the coupling to G proteins. To investigate functional differences between the two dopamine D2 receptor isoforms, we transiently expressed them in cultured cells. To do so we developed an assay to study membrane receptors that are coupled to the adenylyl cyclase. Using this assay, we were able to show that the stimulation of the adenylyl cyclase induced by the activation of the beta 2-adrenergic receptor is inhibited more efficiently by D2B than D2A. The effects elicited by the D2 receptors are mediated by pertussis toxin-sensitive G proteins. Treatment of transfected cells with pertussis toxin abolishes the inhibitory effects in a dose- and receptor isoform-dependent manner. Our results suggest that the two dopamine receptor isoforms are differentially coupled to G proteins. IS - 8 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 0027-8424 AD - Laboratoire de Génétique Moléculaire des Eucaryotes, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine, Strasbourg, France. EP - 3139 TI - Transcription mediated by a cAMP-responsive promoter element is reduced upon activation of dopamine D2 receptors. VL - 88 SP - 3135 KW - camp KW - d2 KW - dopamine KW - promoter KW - transcription AU - Montmayeur, JP AU - Borrelli, E PY - 1991/04/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/1849644 ER -