Angiotensin signaling and receptor types in teleost fish.
Despite advances characterizing mammalian angiotensin receptors, the phylogeny of fish angiotensin receptors remains unclear. Three aspects of receptor function: (1) the nature of the ligand; (2) the second messenger system activated by it; and (3) the pharmacological profile of specific antagonists, are examined to provide insight into the fish receptor. (1) The octapeptide sequences of fish and mammalian angiotensin II (ANG II) are nearly homologous, differing only at the first and fifth residues. Both peptides are almost equally efficacious and equipotent in heterologous systems and both contain key agonist switches Tyr(4) and Phe(8) necessary to activate mammalian AT(1)-type receptors. (2) ANG II increases inositol trisphosphate production, and elevates intracellular calcium in fish tissues consistent with activation of the AT(1) receptor. (3) However, the specific mammalian sartan-type AT(1) antagonists, e.g. losartan, produce inconsistent results in fish often acting as partial agonists, or inhibiting only at elevated concentrations. Because sartans and ANG II act at distinct sites on the AT(1) receptor, we propose that the teleost receptor is an AT(1)-type receptor that is fairly well conserved with respect to both the ANG binding site and coupling to the second messenger system, whereas the sartan binding site has been poorly conserved. The evidence for non-AT(1) type ANG II receptors in teleosts is limited. Mammalian AT(2) receptor antagonists are generally ineffective but may block at elevated, non-specific doses. Truncated ANG II fragments, ANG III and ANG IV, are often less potent than ANG II, however, their receptors have not been examined. Preliminary studies in trout indicate that angiotensin 1-7 may have a mild vasodilatory effect; additional work is needed to determine if non-AT(1)-type receptors are involved.
Russell
M J
MJ
Indiana University School of Medicine, South Bend Center for Medical Education, University of Notre Dame, Indiana 46556, USA.
Klemmer
A M
AM
Olson
K R
KR
D000595:Amino Acid Sequence; D000809:Angiotensins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002490:Central Nervous System / Q000502:physiology; D004326:Drinking / Q000502:physiology; D005399:Fishes / Q000235:genetics / Q000502:physiology*; D005880:Gills / Q000502:physiology; D006801:Humans; D007422:Intestines / Q000502:physiology; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D008322:Mammals; D011945:Receptors, Angiotensin / Q000145:classification / Q000235:genetics / Q000502:physiology*; D017385:Sequence Homology; D015398:Signal Transduction
D000809:Angiotensins; D011945:Receptors, Angiotensin