The AT2 receptor: fact, fancy and fantasy (original) (raw)
Related papers
Hypertension, 2001
Angiotensin II exerts a potent role in the control of hemodynamic and renal homeostasis. Angiotensin II is also a local and biologically active mediator involved in both endothelial and smooth muscle cell function acting on 2 receptor subtypes: type 1 (AT 1 R) and type 2 (AT 2 R). Whereas the key role of AT 2 R in the development of the embryo has been extensively studied, the role of AT 2 R in the adult remains more questionable, especially in humans. In vitro studies in cultured cells and in isolated segments of aorta have shown that AT 2 R stimulation could lead to the production of vasoactive substances, among which NO is certainly the most cited, suggesting that acute AT 2 R stimulation will produce vasodilation. However, in different organs or in small arteries isolated from different type of tissues, other vasoactive substances may also mediate AT 2 R-dependent dilation. Sometimes, such as in large renal arteries, AT 2 R stimulation may lead to vasoconstriction, although it is not always seen. In isolated arteries submitted to physiological conditions of pressure and flow, AT 2 R stimulation may also have a role in shear stress-induced dilation through a endothelial production of NO. Thus, when acutely stimulated, the most probable response expected from AT 2 R stimulation will be a vasodilation. Therefore, in the perspective of a chronic AT 1 R blockade in patients, overstimulation of AT 2 R might be beneficial, given their potential vasodilator effect.
Angiotensin II receptor pharmacology and AT1-receptor blockers
Journal of Human Hypertension, 1999
Angiotensin II (Ang II) has diverse physiological actions leading, for example, to increases in extracellular volume, peripheral vascular resistance and blood pressure, and has also been implicated in the regulation of cell growth and differentiation. Molecular cloning and pharmacological studies have defined two major classes of Ang II receptors, designated as AT 1 and AT 2. Most effects of Ang II are mediated by AT 1 receptors. Much less is known about the physiological role of AT 2 receptors. Recent evidence suggests involvement of AT 2 receptors in development, cell differentiation, apoptosis and regeneration in various tissues. AT 1 and AT 2 recep
International union of pharmacology. XXIII. The angiotensin II receptors
Pharmacological reviews, 2000
The cardiovascular and other actions of angiotensin II (Ang II) are mediated by AT(1) and AT(2) receptors, which are seven transmembrane glycoproteins with 30% sequence similarity. Most species express a single autosomal AT(1) gene, but two related AT(1A) and AT(1B) receptor genes are expressed in rodents. AT(1) receptors are predominantly coupled to G(q/11), and signal through phospholipases A, C, D, inositol phosphates, calcium channels, and a variety of serine/threonine and tyrosine kinases. Many AT(1)-induced growth responses are mediated by transactivation of growth factor receptors. The receptor binding sites for agonist and nonpeptide antagonist ligands have been defined. The latter compounds are as effective as angiotensin converting enzyme inhibitors in cardiovascular diseases but are better tolerated. The AT(2) receptor is expressed at high density during fetal development. It is much less abundant in adult tissues and is up-regulated in pathological conditions. Its signal...
A functional comparison of the rat type-1 angiotensin II receptors (AT1AR and AT1BR)
Regulatory Peptides, 1995
To evaluate and functionally compare the rat ATjA and AT m 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~A receptor is pharmacologically similar to the recombinant ATjB receptor• Functional studies indicate that both receptor subtypes can indepefidently activate the phospholipase C/IP 3 and the dihydropyridinesensitive 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 ATjA and AT m receptors appear to be pharmacologically and functionally similar, the control of their expression seems to be governed by distinct transcription factors.
Modulation of the Vascular Smooth Muscle Angiotensin Subtype 2 (AT2) Receptor by Angiotensin II* 1
Biochemical and …, 1998
The angiotensin subtype 2 (AT 2) receptor is scarce in most adult vascular tissues except after injury. Since angiotensin II (AngII) is released upon injury, we examined the possibility that AngII governs AT 2 receptor expression in smooth muscle cells (SMC). A polyclonal antiserum, raised to a peptide corresponding to the AT 2 receptor C-terminus, recognized a ϳ45-kDa protein after transfection of cos-7 cells with AT 2 receptor cDNA. Detection of a ϳ65-kDa band in extracts of SMC indicated that the AT 2 receptor was glycosylated. Treatment of SMCs with AngII increased AT 2 receptor levels fourfold over 24 h. This response was abrogated by losartan, but not by PD123319, indicating AT 1 receptor involvement. AngII-dependent increases in AT 2 receptor levels were also prevented by LY294002, an inhibitor of phosphatidyinositol 3-kinase, but not by rapamycin. These results indicate AngII influences AT 2 receptor expression through the AT 1 receptor via a signaling pathway that includes PI3K.
The Angiotensin II AT2 Receptor Is an AT1Receptor Antagonist
Journal of Biological …
The vasopressor angiotensin II activates AT 1 and AT 2 receptors. Most of the knownin vivo effects of angiotensin II are mediated by AT 1 receptors while the biological functions of AT 2 receptors are less clear. We report here that the AT 2 receptor binds directly to the AT 1 receptor ...
Peptides, 2005
Angiotensin II (AngII) is considered as a cytokine-like factor displaying a variety of proinflammatory and profibrotic cellular effects. Most of these effects seem mediated by AT1 signaling, whereas AT2 expression and function in adult human cells remain unclear. We have studied AT1 and AT2 expression in different human adult fibroblasts types and analyze their response to AngII. AngII did not induce thymidine incorporation, apoptosis nor collagen gene or protein expression in human fibroblasts. Specific AT1 or AT2 inhibitors did not modify this apparent resistance to AngII. We found abundant expression of both AT1 and AT2 receptors in all human fibroblasts studied, whereas vascular smooth muscle cells (VSMC) which only expressed AT1 receptor, displayed a clear AT1-dependent proliferative response to AngII. These data demonstrate that cultured human adult fibroblasts express both AT1 and AT2 receptor types and this phenomenon is associated with a lack of growth or collagen synthesis responses to AngII.
Angiotensin II AT2 receptor subtype
Journal of Hypertension, 2003
The renin-angiotensin system (RAS) plays a pivotal role in the regulation of fluid, electrolyte balance and blood pressure, and is a modulator of cellular growth and proliferation. Biological actions of RAS are linked to the binding of the effector molecule, angiotensin II (AngII), to specific membrane receptors, mostly the AT 1 subtype and, to a lesser extent, other subtypes. Following the identification and characterization of the AT 2 subtype receptor, it has been proposed that a complex interaction between AngII and its receptors may play an important role in the effects of RAS. In this paper current information on AngII subtype receptors-their structure, regulation and intracellular signalling-are reviewed, with a particular emphasis on the potential relevance for cardiovascular pathophysiology. In addition, we discuss modulation of expression of the AT 2 receptor and its interaction with the AT 1 receptor subtype, as well as the potential effects of this receptor on blood pressure regulation. A better understanding of the integrated effects of the AngII subtype receptors may help to elucidate the function of the RAS, as well as their participation in the mechanisms of cardiovascular disease and attendant therapeutic implications.