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Current Pharmaceutical Design 2013
Topics: Angiotensin Receptor Antagonists; Humans; Receptors, Angiotensin
PubMed: 23176222
DOI: 10.2174/1381612811319170001 -
Comparative Biochemistry and... Jan 2001The cloning of the avian Ang II receptor shows that it is molecularly close to the AT(1)-type mammalian receptor. However, pharmacological characterization in... (Comparative Study)
Comparative Study Review
The cloning of the avian Ang II receptor shows that it is molecularly close to the AT(1)-type mammalian receptor. However, pharmacological characterization in transfected cells shows that, even though the avian receptor is coupled to the phospholipase C, as is the AT(1), its profile of specificity towards antagonists appears different from that of the two angiotensin II mammalian receptor types. The fowl Ang II receptor mRNA is expressed in classical adult target organs for Ang II and, interestingly, also in endothelial cells, but not in vascular smooth muscle cells. In the endothelial cells, it may mediate the peculiar vasorelaxation effect of Ang II already reported in the chicken. The recent description of the expression pattern in the chick embryo shows that the avian Ang II receptor is expressed in many different mesenchymal tissues, a feature which is the signature of the AT(2) mammalian receptor. Altogether, these data imply that the avian Ang II receptor is an atypical receptor that cannot be readily classified as either of the two mammalian Ang II receptor types and, therefore, reinforce the evidence for another Ang II receptor in the avian class.
Topics: Amino Acid Sequence; Animals; Cloning, Molecular; Gene Expression; Humans; Mammals; Molecular Sequence Data; Poultry; RNA, Messenger; Receptors, Angiotensin; Sequence Homology, Amino Acid; Species Specificity
PubMed: 11137440
DOI: 10.1016/s1095-6433(00)00298-1 -
CNS Drugs 2002In addition to the systemic renin-angiotensin system (RAS), a local RAS has been identified. Recent research has focused on this latter system and has investigated the... (Review)
Review
In addition to the systemic renin-angiotensin system (RAS), a local RAS has been identified. Recent research has focused on this latter system and has investigated the effects of locally generated angiotensin II, especially in the kidney, heart and CNS. In the mammalian brain, all components of the RAS are present including angiotensin AT(1) and AT(2) receptor subtypes. While the AT(1) receptor is responsible for the classical effects of angiotensin II, it has been found that the AT(2) receptor displays totally different signalling mechanisms and this has revealed hitherto unknown functions of angiotensin II. AT(2) receptors are expressed at low density in many healthy adult tissues, but are up-regulated in pathological circumstances, e.g. stroke or nerve lesion. Evidence has now emerged that the actions of angiotensin II that are exerted via the AT(2) receptor are directly opposed to those mediated by the AT(1 )receptor. For example, the AT(2) receptor has antiproliferative properties and therefore opposes the growth-promoting effect linked to AT(1) receptor stimulation. It has been reported that the AT(2) receptor regulates several functions of nerve cells, e.g. ionic fluxes, cell differentiation and axonal regeneration, but also modulates programmed cell death. It is possible that a more extensive knowledge of the AT(2) receptor could contribute to the understanding of the clinically beneficial effects of AT(1) receptor antagonists, as this treatment may unmask AT(2) receptor activity. This review presents selected aspects of advances in AT(2) receptor pharmacology, molecular biology and signal transduction with particular reference to possible novel therapeutic options for CNS diseases.
Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Humans; Ligands; Nervous System Diseases; Receptor, Angiotensin, Type 2; Receptors, Angiotensin
PubMed: 11888335
DOI: 10.2165/00023210-200216030-00001 -
American Journal of Hypertension Jun 1992The octapeptide, angiotensin II (Ang II), the biologically active component of the renin-angiotensin system, elicits its multiple actions through the stimulation of... (Review)
Review
The octapeptide, angiotensin II (Ang II), the biologically active component of the renin-angiotensin system, elicits its multiple actions through the stimulation of specific surface receptors on various target organs. Although the existence of Ang II receptor subtypes has been suspected for some time, definitive evidence for Ang II receptor heterogeneity has been obtained only with the recently introduced nonpeptide Ang II receptor antagonists, exemplified by the prototypic compounds DuP 753 and PD 123177. The sites having high affinity for DuP 753 are designated as site 1 (AT1 receptors) and those having a high affinity for PD 123177 as site 2 (AT2 receptors). Unlike Ang I, Ang II, Ang III, and peptide antagonists, such as saralasin, which all are relatively nonselective ligands for both Ang II receptors, the peptides CGP42112A and p-aminophenylalanine6-Ang II show a marked preference for the AT2 site. The occurrence of the AT1 and AT2 receptor subtypes/binding sites identified so far appears widespread. The presence and proportion of these receptors vary significantly among different tissues/organs of the same species and within the same tissue/organ of different species. Despite the abundance of the AT2 site, its functional correlates remain to be determined. The DuP 753-sensitive site (AT1 receptor) mediates all the major Ang II-induced biological effects, including adrenal aldosterone and catecholamine secretion, release of catecholamines from sympathetic ganglia, central nervous system responses, and vasoconstriction.
Topics: Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Binding Sites; Biphenyl Compounds; Drug Resistance; Humans; Imidazoles; Losartan; Oligopeptides; Pyridines; Receptors, Angiotensin; Terminology as Topic; Tetrazoles; Tissue Distribution
PubMed: 1524767
DOI: 10.1093/ajh/5.6.406 -
Journal of the... Sep 2011
Review
Topics: Humans; Models, Biological; Receptor Cross-Talk; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Renin-Angiotensin System; Ventricular Remodeling
PubMed: 21880671
DOI: 10.1177/1470320311417750 -
Advances in Pharmacology (San Diego,... 1994
Review
Topics: Amino Acid Sequence; Angiotensin II; Angiotensin Receptor Antagonists; Animals; Binding Sites; Cloning, Molecular; Gene Expression Regulation; Humans; Molecular Sequence Data; Receptors, Angiotensin; Structure-Activity Relationship
PubMed: 8080819
DOI: 10.1016/s1054-3589(08)60498-6 -
Cell Research Sep 2001The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after... (Review)
Review
The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major component of the renin-angiotensin system (RAS). It mediates the classical biological actions of Ang II. Among the structures required for regulation and activation of the receptor, its carboxyl-terminal region plays crucial roles in receptor internalization, desensitization and phosphorylation. The mechanisms involved in heterotrimeric G-protein coupling to the receptor, activation of the downstream signaling pathway by G proteins and the Ang II signal transduction pathways leading to specific cellular responses are discussed. In addition, recent work on the identification and characterization of novel proteins associated with carboxyl-terminus of the AT1 receptor is presented. These novel proteins will advance our understanding of how the receptor is internalized and recycled as they provide molecular mechanisms for the activation and regulation of G-protein-coupled receptors.
Topics: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Carrier Proteins; Cell Line; Endocytosis; Gene Expression Regulation; Heterotrimeric GTP-Binding Proteins; Humans; Molecular Sequence Data; Protein Structure, Tertiary; Protein Transport; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Recombinant Fusion Proteins; Renin-Angiotensin System; Sequence Alignment; Signal Transduction
PubMed: 11642401
DOI: 10.1038/sj.cr.7290083 -
Journal of Cardiovascular Pharmacology 1990Angiotensin II (Ang II) is a potent effector peptide of the renin-angiotensin system that exerts a wide variety of physiological actions on the cardiovascular, renal,... (Review)
Review
Angiotensin II (Ang II) is a potent effector peptide of the renin-angiotensin system that exerts a wide variety of physiological actions on the cardiovascular, renal, endocrine, and central and peripheral nervous systems. Angiotensin exerts its actions by binding to specific receptors in the plasma membrane of various tissues. Structure-activity relationship studies and competition-binding experiments have identified a potency series of angiotensin analogues. Such studies have demonstrated that target organs display different preferences for Ang II and homologues such as Ang III and des-[Phe8] angiotensin II. Similarly, agents that normally are considered to be pure receptor antagonists for a given response (tissue) are full agonists in other tissues. Indirect evidence obtained from the above studies have led to the speculation that there are multiple angiotensin receptor subtypes among various tissues as well as within single cell types. Multiple mechanisms of signal transduction have been demonstrated for angiotensin. For example, depending on the effector organ, angiotensin stimulates phosphoinositide turnover and release of internal calcium, modulates voltage-dependent calcium channels, directly activates calcium channels, and inhibits adenylate cyclase activity. Recently, the identification of selective, high-affinity peptide and nonpeptide antagonists has resulted in further characterization of angiotensin receptors into distinct subtypes. In addition, dithiothreitol, an agent that reduces disulfide bridges, has been a useful tool in the characterization of angiotensin receptors as the subtypes apparently are not affected equally by this agent. However, further work needs to be performed to characterize angiotensin receptors with respect to heterogeneity, structure, transducing mechanisms, and physiological function.
Topics: Angiotensin II; Animals; Binding Sites; Guinea Pigs; Rabbits; Rats; Receptors, Angiotensin; Structure-Activity Relationship
PubMed: 1705624
DOI: 10.1097/00005344-199016004-00007 -
Nihon Rinsho. Japanese Journal of... Sep 2011Recent clinical studies have shown that RAS inhibitors are effective not only for the prevention of end-organ damage in hypertensive patients, but also for prevention of... (Review)
Review
Recent clinical studies have shown that RAS inhibitors are effective not only for the prevention of end-organ damage in hypertensive patients, but also for prevention of new-onset hypertension, diabetes mellitus, and atrial fibrillation. Vaccines against the RAS have been developed since the 1950s, and a recent phase IIa placebo-controlled study has confirmed that an angiotensin vaccine causes a significant decrease in blood pressure in hypertensive patients. The results of animal experiments from our and other laboratories have suggested that vaccination against the angiotensin type 1 (AT1) receptor causes a significant decrease in blood pressure in animal models of hypertension, and also ameliorates hypertensive end-organ damage. The angiotensin receptor may therefore be an important target for the development of vaccines for the prevention of hypertension and related complications.
Topics: Humans; Hypertension; Receptors, Angiotensin
PubMed: 21922766
DOI: No ID Found -
Kidney International Dec 1994Angiotensin II is an eight amino acid peptide which plays a major role in the regulation of cardiovascular homeostasis. The physiologic effects of angiotensin (Ang) II... (Review)
Review
Angiotensin II is an eight amino acid peptide which plays a major role in the regulation of cardiovascular homeostasis. The physiologic effects of angiotensin (Ang) II are mediated by a G-protein coupled receptor, termed AT1, which activates phospholipase C. A major factor regulating angiotensin II receptor function is the rapid desensitization following agonist stimulation. However, despite years of investigation, the mechanism by which the angiotensin receptor is regulated remains unclear. The cloning of the AT-1 receptor and the availability of cell lines which stabily express this receptor has helped elucidate these mechanisms. In this paper, we review the data from our laboratory concerning the post-translational regulation of the angiotensin receptor function.
Topics: Animals; Cell Line; Cloning, Molecular; Humans; Mice; Receptors, Angiotensin; Signal Transduction; Transfection
PubMed: 7699989
DOI: 10.1038/ki.1994.429