Selective silencing of angiotensin receptor subtype 1a (AT1aR) by RNA interference.
Angiotensin II exerts its physiological effects by activating multiple subtypes of its receptor such as AT1a-, AT1b-, and AT2-receptors. Because of a high degree of similarity among these G-protein-coupled receptors, it has been difficult to assign diverse physiological actions of angiotensin II through these receptor subtypes. We have developed small interfering RNAs to selectively inhibit the expression of the AT1a receptor (AT1aR) subtype. A dsRNA, AT1 47, was found to be highly selective and efficient in reducing the levels of AT1aR subtype. Transfection of AT1aR-expressing CHO cells with dsRNA AT1 47 resulted in an 80% decrease in the AT1aR expression. In contrast, dsRNA AT1 47 showed no significant effects on both AT1bR and AT2R subtypes. Thus, AT1 47 provides us with a powerful tool to selectively silence this subtype of receptor to investigate its role in cardiovascular physiology.
Vázquez
Jorge
J
Department of Physiology and Functional Genomics, College of Medicine, University of Florida, McKnight Brain Institute, Gainesville, FL 32610, USA.
Correa de Adjounian
María F
MF
Sumners
Colin
C
González
Aaron
A
Diez-Freire
Carlos
C
Raizada
Mohan K
MK
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D020868:Gene Silencing; D017136:Ion Transport / Q000187:drug effects; D011485:Protein Binding; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000494:pharmacology*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011993:Recombinant Fusion Proteins; D000804:Angiotensin II; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D002118:Calcium