A functional comparison of the rat type-1 angiotensin II receptors (AT(1A)R and AT(1B)R)

被引:29
|
作者
Martin, MM
White, CR
Li, HB
Miller, PJ
Elton, TS
机构
[1] BRIGHAM YOUNG UNIV,DEPT CHEM & BIOCHEM,PROVO,UT 84602
[2] UNIV ALABAMA,DEPT MED,VASC BIOL & HYPERTENS PROGRAM,BIRMINGHAM,AL 35294
关键词
stable cell line; losartan; signal transduction;
D O I
10.1016/0167-0115(95)00123-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To evaluate and functionally compare the rat AT(1A) and AT(1B) receptor subtypes, stable Chinese hamster ovary (CHO) cell lines expressing either recombinant receptor in approximately equal numbers were generated. Radioligand binding data suggests that the recombinant AT(1A) receptor is pharmacologically similar to the recombinant AT(1B) receptor. Functional studies indicate that both receptor subtypes can independently activate the phospholipase C/IP3 and the dihydropyridine-sensitive voltage-dependent Ca2+ channel signal transduction pathways with equal efficiency, but are unable to modulate cAMP accumulation under our experimental conditions, Furthermore, both receptors can be directly involved in the cellular growth properties of All. Slot-blot experiments clearly demonstrate that these receptors are expressed in a tissue-specific manner. A sequence comparison of the 5' flanking regions of these two genes shows that they have very little sequence homology (similar to 36%), suggesting that although the AT(1A) and AT(1B) receptors appear to be pharmacologically and functionally similar, the control of their expression seems to be governed by distinct transcription factors.
引用
收藏
页码:135 / 147
页数:13
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