A chimeric D2 dopamine/ml muscarinic receptor with D2 binding specificity mobilizes intracellular calcium in response to dopamine
- 11 February 1991
- journal article
- Published by Wiley in FEBS Letters
- Vol. 279 (1) , 87-90
- https://doi.org/10.1016/0014-5793(91)80257-4
Abstract
Using PCR methodology, a chimeric receptor cDNA was constructed in which the entire third cytoplasmic loop of the human D2 dopamine receptor was replaced by the analogous portion of the human ml muscarinic receptor. When expressed in CHO cells, the chimeric D2/ml receptor bound dopaminergic ligands with affinities similar to the native D2(414) receptor. Intracellular calcium levels (measured with Furu-2) were not altered when CHO cells expressing the D2(414) receptor were exposed to dopamine. In contrast, dopamine elevated intracellular calcium levels in cells expressing the D2/ml chimeric receptor in a dose-dependent manner which was blocked by the D2 antagonist, fluphenazine. The ability to construct G-protein-linked receptor chimeras which mobilize calcium with nearly unaltered pharmacologic specificity raises the possibility of a generic strategy for creating non-radioisotopic reporter systems for use in drug discoveryKeywords
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