Comparative analysis of amphibian and mammalian angiotensin receptors

Amphibian angiotensin receptors (xAT receptors) share many similarities with mammalian type 1 angiotensin receptors (AT(1) receptors). Both xAT and AT(1) receptors belong to the super family of seven transmembrane spanning G protein-coupled receptors and share approximately 60% amino acid homology. Highly stable secondary structure in the 5' leader sequences and the presence of the mRNA destabilizing sequence (AUUUA) in the 3' untranslated region (3'UTR) of the xAT and AT(1) receptor mRNAs suggest similar mechanisms exist for regulating gene expression. Amphibian and mammalian AT receptors bind angiotensin with equivalent affinities but show marked differences in their affinities towards mammalian AT(1) receptor subtype selective non-peptide ligands. Both xAT and AT(1) receptors couple to G proteins and to the phospholipase C (PLC) signal transduction pathway. Mammalian AT(1) receptors play a key role in maintaining blood pressure and fluid homeostasis and there is considerable evidence that xAT receptors play a similarly important role in amphibians. This review focuses on the comparison of amphibian xAT receptors with mammalian AT(1) receptors in terms of their structure, pharmacology, signaling, and function.