Receptors and their classification: focus on angiotensin II and the AT2 receptor

Csikós, Tamá; Chung, Oliver; Unger, Th.

doi:10.1038/sj.jhh.1000639

Cited by 74 publications

(49 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of AT 1 receptor antagonist may not be entirely due to blockade of the AT 1 receptor. 84 When AT 1 receptor is blocked, plasma renin and angiotensins increase, 85 and therefore increased angiotensins may act preferably on AT 2 receptor (Figure 3). If the AT 2 receptor contributes to the pathogenesis and consequent remodeling of cardiovascular diseases in humans, AT 1 receptor antagonist may have some specific effects in the treatment of cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Recent Progress in Angiotensin II Type 2 Receptor Research in the Cardiovascular System

1999

View full text Add to dashboard Cite

Abstract-Angiotensin II (Ang II) plays an important role in regulating cardiovascular hemodynamics and structure.Multiple lines of evidence have suggested the existence of Ang II receptor subtypes, and at least 2 distinct receptor subtypes have been defined on the basis of their differential pharmacological and biochemical properties and designated as type 1 (AT 1 ) and type 2 (AT 2 ) receptors. To date, most of the known effects of Ang II in adult tissues are attributable to the AT 1 receptor. Recent cloning of the AT 2 receptor contributes to reveal its physiological functions, but many functions of the AT 2 receptor are still an enigma. AT 1 and AT 2 receptors belong to the 7-transmembrane, G protein-coupled receptor family. However, accumulating evidence demonstrates that the function and signaling mechanisms of these receptor subtypes are quite different, and these receptors may exert opposite effects in terms of cell growth and blood pressure regulation. We will review the role of the AT 2 receptor in the cardiovascular system and the molecular and cellular mechanisms of AT 2 receptor action. (Hypertension. 1999;33:613-621.)Key Words: angiotensin II Ⅲ apoptosis Ⅲ blood vessels Ⅲ cell growth Ⅲ heart Ⅲ receptors Ⅲ signaling A ngiotensin II (Ang II) has significant influence on the heart and blood vessels through its effects on systemic hemodynamics and blood volume. Ang II also exerts longterm structural effects through its direct hypertrophic and proliferative growth actions. 1,2 Multiple lines of evidence have suggested the existence of Ang II receptor subtypes, but it was only recently that at least 2 distinct receptor subtypes were defined on the basis of their differential pharmacological and biochemical properties and designated as type 1 (AT 1 ) and type 2 (AT 2 ) receptors. 3,4 Subsequent cloning of these 2 receptors 5-8 fostered renewed interest in the biochemistry, pharmacology, and physiology of Ang II receptors.To date, extensive pharmacological evidence indicates that most of the known effects of Ang II in adult cardiovascular tissues are attributable to the AT 1 receptor, but less is known about the AT 2 receptor. As shown in the Table, accumulating evidence revealed that this receptor acts as an antagonistic receptor against AT 1 receptor, ie, AT 2 receptor exerts antigrowth, antihypertrophic, and proapoptotic effects. Vascular Effect Vascular DevelopmentIt has been shown that rat and mouse vascular AT 2 receptor mRNA is expressed at very low levels in the aorta during early embryonic development (up to embryonic day 15) but at high levels during the later stages of development (embryonic days 16 to 21) and in the neonate, 9,10 whereas the AT 1 receptor in aorta is expressed at relatively constant levels from the first point tested (embryonic day 10) throughout development and the neonatal period and into the adult stage. After birth, AT 2 receptor levels decline rapidly. Shanmugam et al 11 confirmed this observation using in situ hybridization. The high level of AT 2 receptor mRNA expression ...

show abstract

Section: Discussionmentioning

confidence: 99%

Recent Progress in Angiotensin II Type 2 Receptor Research in the Cardiovascular System

1999

View full text Add to dashboard Cite

show abstract

“…45 The binding of angiotensin II to specific extracellular sites on the AT 1 receptor results in the activation of phospholipases C, D and A 2 via the G protein (G q ) or inhibition of adenylate cyclase via the G protein (G i ). 42,46,47 Phospholipase C activation results in the generation of 1,4,5-triphosphate and diacylglycerol, the subsequent activation of protein kinase C and an increase in intracellular calcium. 42 The rise in intracellular calcium is associated with…”

Section: Characterisation Of the Angiotensin II Receptorsmentioning

confidence: 99%

Blocking the tissue renin-angiotensin system: the future cornerstone of therapy

Unger

Azizi

Gg³

2000

J Hum Hypertens

View full text Add to dashboard Cite

The development of angiotensin-converting enzyme inhibitors and selective angiotensin type 1 (AT 1 )-receptor antagonists has provided new insights into understanding the mechanism of the renin-angiotensin system (RAS) in the pathophysiology of cardiovascular disease. There is good evidence from meta-analyses that shows that inhibition of the RAS achieves organ protection features that go beyond blood pressure control. Candesartan cilexetil, a new angiotensin II receptor

show abstract

“…The resultant complex then binds directly to response elements present on various genes (Nilsson et al 2001) or modifies transcription through protein-protein interactions prior to DNA binding (Pfahl 1993). When ER binds to E2, it undergoes a conformational change that results in dimerization, binding to specific DNA elements, and transcriptional regulation of target genes (Nahmias & Strosberg 1995, Csikos et al 1998. It is becoming increasingly clear, however that multiple ligands for the steroid receptor superfamily can modulate cell function through nongenomic actions mediated through plasma-membrane proteins (Blackmore et al 1991, Nemere et al 1994, Wehling 1995.…”

Section: Introductionmentioning

confidence: 99%

Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells

Gilad

Bresler²,

J³

et al. 2005

Journal of Endocrinology

View full text Add to dashboard Cite

We previously demonstrated that 17 -estradiol (E2) regulates the transcription and expression of the vitamin D receptor (VDR) in rat colonocytes and duodenocytes in vivo. The aim of the present study was to assess whether the extracellular signal-regulated kinase (ERK) induced by E2 is involved in regulating VDR expression. We compared E2-associated signaling activity in HT29 colon cancer cells, a non-classical E2-target, with that in MCF-7 breast cancer cells, the natural targets of the hormone. E2 did not affect proliferation of HT29 cells, but enhanced proliferation of MCF-7 cells. Vitamin D inhibited proliferation of both cell lines and the combined treatment induced potentiation of vitamin D activity. E2 upregulated VDR transcription and protein expression concomitantly with ERK 1/2 phosphorylation in both cell lines. PD98059, a specific mitogen-activated protein kinase (MAPK) inhibitor, prevented E2-mediated activation of ERK 1/2, with concomitant inhibition of VDR expression. ICI182780 inhibited VDR expression in HT29 and MCF-7 cell lines. A conjugate of E2 and bovine serum albumin upregulated phosphorylation of ERK 1/2 and concomitantly enhanced VDR expression in a similar fashion as the nonconjugated hormone. Expression of ER and ER was detected in MCF-7 and HT29 cell lines respectively, which localized to the nuclei, cytosol and caveolar membrane rather than non-caveolar membrane. Disruption of lipid rafts/caveolae by depleting cellular cholesterol with the cholesterol-binding reagentmethylcyclodextrin blocked ERK 1/2 phosphorylation concomitantly with VDR upregulation. The tyrosine phosphorylation inhibitor suramin and src kinase inhibitor PP2 inhibited both ERK 1/2 phosphorylation and VDR expression. E2 induced phosphorylation of Raf and Jun in a time-dependent manner. The Ras/Raf dependent inhibitor of transactivation sulindac sulfide also blocked E2 effects. The specific c-Jun phosphorylation inhibitor SP600125 dose dependently inhibited c-Jun phosphorylation and VDR expression. The MAPK/ERK kinase inhibitor PD 98059 downregulated both c-Jun phosphorylation and VDR expression indicating that upstream and downstream events in the signaling cascade are all related to the control of VDR expression. Taken together, our data suggest that E2 binds to receptors compartmentalized to membranal caveolar domains in HT29 and MCF-7 cells, inducing ERK 1/2 activation and transcriptional activity, which finally results in upregulation of expression of the VDR gene.

show abstract

Receptors and their classification: focus on angiotensin II and the AT2 receptor

Cited by 74 publications

References 77 publications

Recent Progress in Angiotensin II Type 2 Receptor Research in the Cardiovascular System

Recent Progress in Angiotensin II Type 2 Receptor Research in the Cardiovascular System

Blocking the tissue renin-angiotensin system: the future cornerstone of therapy

Regulation of vitamin D receptor expression via estrogen-induced activation of the ERK 1/2 signaling pathway in colon and breast cancer cells

Contact Info

Product

Resources

About