A functional comparison of the rat type-1 angiotensin II receptors (AT1AR and AT1BR)

To evaluate and functionally compare the rat AT1A and AT1B 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 AT1A receptor is pharmacologically similar to the recombinant AT1B 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 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 (approximately 36%), suggesting that although the AT1A and AT1B receptors appear to be pharmacologically and functionally similar, the control of their expression seems to be governed by distinct transcription factors.