Identification of a fourth angiotensin AT1 receptor subtype in rat

Angiotensin II is a major regulator of cardiovascular function, fluid homeostasis and also plays a role in long-term cardiovascular disease processes. At present it is unclear if and how the diverse functions of angiotensin II may relate to different cellular receptors for this vasoactive peptide. In order to identify subtypes of angiotensin receptors we used a PCR-mediated cloning approach. Oligonucleotide sequences for PCR amplification of angiotensin receptors were selected on the basis of nucleotide sequences conserved between species. Since the coding regions of AT1-type receptors appear to be located on a single exon, we used genomic DNA as a template in the PCR reactions. Resulting amplification products represented a mixture of four different sequences as assessed by T-tracking and sequencing of the partial clones. Three of the clones encode for sequences already known, whereas the fourth clone encoded a novel receptor subtype which we have termed AT1C. Deduced amino acid sequences of the four different receptor subtypes are highly homologous. The AT1C receptor nucleotide sequence homology was greatest to the described AT3 receptor (95%) and less so to the published AT1A (90%) and AT1B (82%) receptor subtypes. The variety and tissue- specific expression of AT1 receptor subtypes and coexpression of different receptor subtypes may account for the diverse tissue- specific actions of angiotensin.