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

Abstract

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 IP 3 and the dihydropyridine-sensitive voltage-dependent Ca 2+ 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 AII. 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 (∼ 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.