D-1A, D-1B, AND D-1C DOPAMINE-RECEPTORS FROM XENOPUS-LAEVIS

Three distinct genes encoding members of the D-1 dopamine receptor family were isolated from Xenopus laevis. Based on the deduced amino acid sequence, two of the receptors (Xen D-1A and Xen D-1B) appear to be homologues of mammalian D-1/D-1A and D-5/D-1B receptors. The third receptor, termed Xen Diet displays equal overall amino acid and nucleotide sequence identity (approximate to 55%) with mammalian D-1A and D-1B/D-5 receptors. In agreement with their structural similarities, Xen D-1A and D-1B receptors, when expressed in COS-7 cells, displayed pharmacological profiles that paralleled those of their mammalian counterparts, with dopamine and 2-amino-6,7-dihydroxytetralin exhibiting 10-fold higher affinity for D-1B than for D-1A. The Xen D-1C receptor displayed an overall rank order of potency and pharmacological profile clearly indicative of a D-1-like receptor, with individual affinities for most agonists higher than those for either Xen or mammalian D-1/D-1A and D-5/D-1B receptors, whereas antagonist Ki values were intermediate to those for the D-1/D-1A and D-5/D-1B receptors. All three receptors stimulated adenylate cyclase activity in response to dopamine or SKF-82526. Xen D-1A, D-1B, and D-1C receptor mRNAs were differentially distributed, with all three receptors expressed in brain and only D-1B and D-1C receptors expressed in kidney. The existence of a receptor which lacks appreciable overall sequence similarity to, but displays pharmacological homology with, mammalian D-1-like receptors lends strong support to the contention that additional mammalian D-1-like receptor gene products may exist to allow for the expression of the full spectrum of D-1-like dopamine receptor-mediated events.