A FUNCTIONAL COMPARISON OF THE RAT TYPE-1 ANGIOTENSIN-II RECEPTORS (AT(1A)R AND AT(1B)R)

To evaluate and functionally compare the rat AT(1A) and AT(1B) recepto r subtypes, stable Chinese hamster ovary (CHO) cell lines expressing e ither recombinant receptor in approximately equal numbers were generat ed. Radioligand binding data suggests that the recombinant AT(1A) rece ptor is pharmacologically similar to the recombinant AT(1B) receptor. Functional studies indicate that both receptor subtypes can independen tly activate the phospholipase C/IP3 and the dihydropyridine-sensitive voltage-dependent Ca2+ channel signal transduction pathways with equa l efficiency, but are unable to modulate cAMP accumulation under our e xperimental conditions, Furthermore, both receptors can be directly in volved in the cellular growth properties of All. Slot-blot experiments clearly demonstrate that these receptors are expressed in a tissue-sp ecific manner. A sequence comparison of the 5' flanking regions of the se two genes shows that they have very little sequence homology (simil ar to 36%), suggesting that although the AT(1A) and AT(1B) receptors a ppear to be pharmacologically and functionally similar, the control of their expression seems to be governed by distinct transcription facto rs.