The rat angiotensin II AT 1A receptor couples with three different signal transduction pathways

Abstract

To examine whether the subpopulation of the rat type 1 angiotensin II (AII) receptor (AT 1A) couples with a single or multiple signal transduction pathways, we constructed Chinese hamster ovary (CHO) cell lines producing the recombinant receptor. The expressed AT 1A receptor exhibits typical pharmacological characteristics of the AT 1 receptor, known to mediate the main physiological functions of AII. Addition of AII to the CHO cells induced a rapid, transient increase in intracellular free Ca 2+ concentrations ([Ca 2+] i) followed by a lower, sustained phase. Nicardipine, a blocker of voltage-dependent L-type Ca 2+ channels, attenuated the transient [Ca 2+] i response and abolished the sustained phase. The transient phase was also reduced dose-dependently by the phospholipase C inhibitor neomycin. Furthermore, AII inhibited forskolin-evoked cAMP accumulation. These data suggest, although another subpopulation named AT 1B is present, that the rat AT 1A receptor can independently couple with all three signal transduction pathways known to be induced by AII: i. e., i) activation of phospholipase C resulting in InsP 3 generation with a subsequent release of intracellularly stored Ca 2+, ii) activation of dihydropyridine-sensitive voltage-dependent Ca 2+ channels, and iii) inhibition of adenylate cyclase activity.