Angiotensin II receptor type 1
Angiotensin II receptor type 1 or AT receptor is the best characterized angiotensin receptor. It has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor antagonists are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure. Function. The AT receptor mediates the major cardiovascular effects of angiotensin II. Effects include vasoconstriction, aldosterone synthesis and secretion, increased vasopressin secretion, cardiac hypertrophy, augmentation of peripheral noradrenergic activity, vascular smooth muscle cells proliferation, decreased renal blood flow, renal renin inhibition, renal tubular sodium  reuptake, modulation of central sympathetic nervous system activity, cardiac contractility, central osmocontrol and extracellular matrix formation. Mechanism. The angiotensin receptor is activated by the vasoconstricting peptide angiotensin II. The activated receptor in turn couples to G and thus activates phospholipase C and increases the cytosolic Ca concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C. Activated receptor also inhibits adenylate cyclase and activates various tyrosine kinases. Clinical significance. The AT receptor may play role in the generation of reperfusion arrhythmias following restoration of blood flow to ischemic or infarcted myocardium. The AT receptor has also  been implicated in post-traumatic stress disorder, Animal studies. AT receptor antagonists have been shown to reduce fear memory recall in mice. Gene. It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. At least four transcript variants have been described for this gene. Additional variants have been described but their full-length nature has not been determined. The entire coding sequence is contained in the terminal exon and is present in all transcript variants. Huge number of polymorphisms is reported in  the databases for AT1R which provide an avenue to explore these polymorphisms for their implications in protein structure, function and drug efficacy. Methods In the current study all the SNPs (10234) reported in NCBI were analyzed and SNPs which were important in protein structure and drug interactions were identified. Structures of these polymorphic forms were modeled and in silico drug interaction studies were carried out. Results Result of the interaction studies with polymorphism was in correlation with the reported case. Two SNP mutated structures of AT1R i.e. rs780860717 (G288T), rs868647200 (A182C) shows considerably less binding affinities in case of  all angiotensin receptor blockers (ARBs). Interactions. Angiotensin II receptor type 1 has been shown to interact with Zinc finger and BTB domain-containing protein 16. The protein's mRNA has been reported to interact with Mir-132 microRNA as part of an RNA silencing mechanism that reduces receptor expression.