Modulation of the rat angiotensin type 1a receptor by an upstream short open reading frame.

Abstract The rat angiotensin type 1a receptor (AT1aR) is a peptide hormone G protein-coupled receptor (GPCR) that plays a key role in electrolyte homeostasis and blood pressure control. There is a highly conserved short open reading frame (sORF) in exon 2 (E2) that is downstream from exon 1 (E1) and upstream of the AT1aR coding region located in exon 3 (E3). To determine the role of this E2 sORF in AT1aR signaling, human embryonic kidney-293 (HEK293) cells were transfected with plasmids containing AT1aR cDNA with either an intact or disrupted E2 sORF. The intact sORF attenuated the efficacy of angiotensin (Ang) II (p