Tissular expression and regulation of type 1 angiotensin II receptor subtypes by quantitative reverse transcriptase-polymerase chain reaction analysis.

Abstract

Recent studies have revealed that angiotensin II (Ang II) interacts with two pharmacologically different types of seven-transmembrane domain receptors, hence named Ang II type 1 and type 2 (AT, and AT 2 ) receptors. cDNAs for the AT, receptor have been cloned, and the existence of two receptor subtypes, AT, A and AT 1B , has been revealed in rat and mouse. This study presents a new approach for the specific quantification of AT, A and AT, B receptor mRNAs by reverse transcription and polymerase chain reaction amplification in the presence of an AT, receptor mutant cRNA as internal standard. Absolute quantities of mRNA are then determined by extrapolation using the standard curve generated with the internal standard. Moreover, addition of this internal standard to each tube controls for both reverse transcription and polymerase chain reaction amplification in each sample. In male Wistar rats, the highest absolute AT, A receptor mRNA levels were found in liver and kidney and those for AT 1B receptor mRNA in the pituitary. Expressed as a percentage of total AT, A +AT, B A ngiotensin II (Ang II) is a biologically active peptide of the renin-angiotensin system that produces vasoconstriction, aldosterone secretion, catecholamine release, thirst, and prolactin and corticotropin secretions as well as stimulates hypertrophy of vascular smooth muscle cells. © 1994 American Heart Association, Inc.receptor mRNA content, AT, A receptor mRNA content was 100% in liver, 85% in lung, 73% in kidney, 65% in aorta, 48% in adrenals, and 15% in the hypophysis. Since this approach can determine absolute AT, A and AT, B receptor mRNA quantities in different organs, it allows the study of the regulation of their expression under different pathophysiological conditions. After sodium depletion, known to induce hyperactivity of the reninangiotensin system, adrenal AT, A and AT 1B receptor mRNA levels were increased by 60% and 110%, respectively. In contrast, in renovascular hypertension (two-kidney, one clip), also associated with elevated circulating plasma renin activity, adrenal AT 1B receptor mRNA levels decreased by 50%, whereas there was no change in those of AT, A . Therefore, the differential distribution and regulation of these two receptor subtypes suggest that each of them might be involved in the mediation of different biological effects of Ang II. (Hypertension. 1994^4:538-548.)

Angiotensin II‐elicited signal transduction via AT1 receptors in endothelial cells

“…These differences in AT2 receptor expression could be due, at least in part, to differences in culture conditions and in the growth state of the cells, quiescent or proliferating. Indeed, it has been shown that growth factors down-regulate the expression of AT2 but not that of AT, (Kambayashi et al, 1993), and we have detected minimal quantities of the AT2 receptor mRNA by RT-PCR in (Viswanathan et al, 1991;Llorens-Cortes et al, 1994). Both subtypes, ATIA and ATLB, have been found in the whole aorta (LlorensCortes et al, 1994) In turn, IP3 increases the release of Ca2+ from intracellular stores and diacylglycerol activates protein kinase C (Dostal et al, 1990;Sadoshima & Izumo, 1993).…”

“…They have very similar amino acid sequences, pharmacological specificities and signal transductions . It is currently unknown whether the two subtypes have different specific functions, but they have different patterns of expression in tissues (Gasc et al, 1994;Llorens-Cortes et al, 1994), suggesting that they could mediate different physiological functions.…”

Susceptibility to T Cell-Mediated Injury in Immune Complex Disease Is Linked to Local Activation of Renin-Angiotensin System: The Role of NF-AT Pathway

“…In this disease, dose-dependent activation of intrarenal and systemic RAS has been demonstrated (15)(16)(17). AngII has some cellular effects on most tissues, mainly via AT1, that may contribute to the disease pathogenesis (11,19), and also regulates cellular immunity by acting on the proliferation of splenic lymphocytes (20). However, in a cutaneous DTH, AT1 deficiency did not alter the responsiveness, in accordance with a previous study (21), and we failed to find any difference between ␥ Ϫ/Ϫ mice with or without nephritis, suggesting that systemic RAS activation in this disease may not play a significant role in general T cell function.…”

“…In rodents, AT1 exists in two isoforms, AT1A and AT1B, regulated by two different genes. The murine AT1A is the isoform predominantly expressed in most tissues (19). AngII via AT1A triggers the proliferation of splenic lymphocytes following systemic cellular immune responses in mice (20).…”

Blood pressure and renal hemodynamic effects of angiotensin fragments

“…AT 1a receptors are more abundant in the kidney than AT 1b . 20 AT 1a receptors are also expressed in the liver, adrenal gland, ovary, heart, aorta, lung, testis, brain, adipose tissue and vascular smooth muscle, whereas AT 1b receptors are confined to the adrenal gland, brain and testis. 21 AT 2 receptors are highly expressed during fetal development and in newborn mammalian kidneys, with very little expression in the adult mammalian kidney.…”