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

被引:66
作者
SUGAMORI, KS
DEMCHYSHYN, LL
CHUNG, M
NIZNIK, HB
机构
[1] CLARKE INST PSYCHIAT,MOLEC NEUROBIOL LAB,TORONTO M5T 1R8,ON,CANADA
[2] UNIV TORONTO,DEPT PSYCHIAT,TORONTO M5T 1R8,ON,CANADA
[3] UNIV TORONTO,DEPT PHARMACOL,TORONTO M5T 1R8,ON,CANADA
关键词
D O I
10.1073/pnas.91.22.10536
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:10536 / 10540
页数:5
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