The AT2 receptor:: fact, fancy and fantasy

被引:124
作者
de Gasparo, M [1 ]
Siragy, HM
机构
[1] Novartis Phama AG, Basel, Switzerland
[2] Univ Virginia, Dept Med, Charlottesville, VA USA
关键词
angiotensin; angiotensin receptor antagonist; apoptosis; brain; collagen; fibrosis; heart; kidney; proliferation; reproduction; signaling; vessel;
D O I
10.1016/S0167-0115(99)00023-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The angiotensin AT(2) receptor subtype was recently cloned and pharmacologically characterized but its function still remains elusive and controversial. It is a member of the G-protein coupled receptor superfamily with a minimal sequence homology with the AT(1) receptor. responsible for the known effect of angiotensin II. The AT(2) receptor displays a totally different signaling mechanisms from the AT(1) receptor and involves various phosphatases. It is expressed at low density in adult tissues but up-regulated in pathological circumstances. Clearly, the AT(2) receptor has antiproliferative properties and therefore opposes the growth promoting effect linked to the AT(1) receptor stimulation. It is also reported that the AT(2) receptor regulates ionic fluxes, affects differentiation and nerve regeneration, has anti-angiogenic and anti-fibrotic properties and stimulates apoptosis. However, the results, although suggestive, are sometimes equivocal. Obviously, the AT(2) receptor plays a role in the pathogenesis and remodeling of cardiovascular and renal diseases. A more extensive knowledge of the AT(2) receptor could therefore contribute to the understanding of the clincial beneficial effects of the AT(1) receptor antagonists. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:11 / 24
页数:14
相关论文
共 151 条
[1]   Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole [J].
Arima, S ;
Endo, Y ;
Yaoita, H ;
Omata, K ;
Ogawa, S ;
Tsunoda, K ;
Abe, M ;
Takeuchi, K ;
Abe, K ;
Ito, S .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (11) :2816-2823
[2]   Apoptosis in restenosis versus stable-angina atherosclerosis -: Implications for the pathogenesis of restenosis [J].
Bauriedel, G ;
Schluckebier, S ;
Hutter, R ;
Welsch, U ;
Kandolf, R ;
Lüderitz, B ;
Prescott, MF .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (07) :1132-1139
[3]   Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase [J].
Bedecs, K ;
Elbaz, N ;
Sutren, M ;
Masson, M ;
Susini, C ;
Strosberg, AD ;
Nahmias, C .
BIOCHEMICAL JOURNAL, 1997, 325 :449-454
[4]   APOPTOSIS OF HUMAN VASCULAR SMOOTH-MUSCLE CELLS DERIVED FROM NORMAL VESSELS AND CORONARY ATHEROSCLEROTIC PLAQUES [J].
BENNETT, MR ;
EVAN, GI ;
SCHWARTZ, SM .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (05) :2266-2274
[5]   Calcium - a life and death signal [J].
Berridge, MJ ;
Bootman, MD ;
Lipp, P .
NATURE, 1998, 395 (6703) :645-648
[6]  
BLEUEL A, 1995, J NEUROSCI, V15, P750
[7]   Role of type 1 and type 2 angiotensin receptors in angiotensin II-induced cardiomyocyte hypertrophy [J].
Booz, GW ;
Baker, KM .
HYPERTENSION, 1996, 28 (04) :635-640
[8]   ANGIOTENSIN-II AT2 RECEPTORS DO NOT INTERACT WITH GUANINE-NUCLEOTIDE BINDING-PROTEINS [J].
BOTTARI, SP ;
TAYLOR, V ;
KING, IN ;
BOGDAL, Y ;
WHITEBREAD, S ;
DEGASPARO, M .
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1991, 207 (02) :157-163
[9]   THE ANGIOTENSIN-AT2 RECEPTOR STIMULATES PROTEIN TYROSINE PHOSPHATASE-ACTIVITY AND MEDIATES INHIBITION OF PARTICULATE GUANYLATE-CYCLASE [J].
BOTTARI, SP ;
KING, IN ;
REICHLIN, S ;
DAHLSTROEM, I ;
LYDON, N ;
DEGASPARO, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 183 (01) :206-211
[10]   ROLE OF ANGIOTENSIN-II AND PROSTAGLANDIN E(2) IN REGULATING CARDIAC FIBROBLAST COLLAGEN TURNOVER [J].
BRILLA, CG ;
ZHOU, GP ;
RUPP, H ;
MAISCH, B ;
WEBER, KT .
AMERICAN JOURNAL OF CARDIOLOGY, 1995, 76 (13) :D8-D13