Angiotensin signaling and receptor types in teleost fish

Despite advances characterizing mammalian angiotensin receptors, the phylog eny of fish angiotensin receptors remains unclear. Three aspects of recepto r function: (1) the nature of the ligand; (2) the second messenger system a ctivated by it; and (3) the pharmacological profile of specific antagonists , are examined to provide insight into the fish receptor. (1) The octapepti de sequences of fish and mammalian angiotensin II (ANG II) are nearly homol ogous, differing only at the first and fifth residues. Both peptides are al most equally efficacious and equipotent in heterologous systems and both co ntain key agonist switches Tyr(4) and Phe(8) necessary to activate mammalia n AT(1)-type receptors. (2) ANG II increases inositol trisphosphate product ion, and elevates intracellular calcium in fish tissues consistent with act ivation of the AT(1) receptor. (3) However, the specific mammalian sartan-t ype AT(1) antagonists, e.g. losartan, produce inconsistent results in fish often acting as partial agonists, or inhibiting only at elevated concentrat ions. Because sartans and ANG II act at distinct sites on the AT(1) recepto r, we propose that the teleost receptor is an AT(1)-type receptor that is f airly well conserved with respect to both the ANG binding site and coupling to the second messenger system, whereas the sartan binding site has been p oorly conserved. The evidence for non-AT(1) type ANG II receptors in teleos ts is limited. Mammalian AT(2) receptor antagonists are generally ineffecti ve but may block at elevated, non-specific doses. Truncated ANG II fragment s, ANG III and ANG IV, are often less potent than ANG II, however, their re ceptors have not been examined. Preliminary studies in trout indicate that angiotensin 1-7 may have a mild vasodilatory effect; additional work is nee ded to determine if non-AT(1)-type receptors are involved. (C) 2001 Elsevie r Science Inc. All rights reserved.