Singular contributions of fish neuroendocrinology to mammalian regulatory peptide research

During the past 20 years, several bioactive peptides have been identified i n teleost fishes that subsequently have been shown to play important regula tory roles in mammalian physiology. The urophysis, corpuscles of Stannius a nd Brockmann body are anatomical structures particular to fish that have no obvious counterpart in mammals. Extracts and/or cDNA libraries prepared fr om these tissues have been used to identify for the first time urotensin II (U-II), urotensin-I (U-I), stanniocalcin and glucagon-like peptide-1 (GLP- 1). Although U-II and U-I were originally regarded as exclusively the produ cts of the teleost urophysis, the peptides have a wide phylogenetic distrib ution across the vertebrate lineage, including mammals. U-II is localized t o motor neurones in the human spinal cord and is a potent vasoconstrictor t hat may be implicated in the pathogenesis of heart failure. The human ortho log of urotensin-I is urocortin which is synthesized in selected regions of the brain and is the endogenous ligand for the CRF type 2 receptor. Urocor tin is believed to important in mediating the effects of stress on appetite . Stanniocalcin is involved in maintaining calcium and phosphate homeostasi s in teleost fish. An ortholog of stanniocalcin has a widespread distributi on in mammalian tissues and is postulated to regulate renal phosphate excre tion and to protect neurons against damage during cerebral ischemia. The bi ological actions and therapeutic potential of GLP-1 in humans are now fully appreciated but the peptide was first identified as a domain in a preprogl ucagon cDNA prepared from anglerfish Brockmann bodies. In contrast to mamma lian preproglucagons, GLP-1 is present in anglerfish preproglucagon as the bioactive, truncated sequence [corresponding to human GLP-1(7-37)] rather t han the inactive, N-terminally extended form [corresponding to GLP-1(1-37)] . Failure to appreciate the significance of this fact retarded progress in the field for several years. (C) 2000 Elsevier Science BN. All rights reser ved.