SPECIAL EVOLUTION OF NEUROHYPOPHYSEAL HORMONES IN CARTILAGINOUS FISHES - ASVATOCIN AND PHASVATOCIN, 2 OXYTOCIN-LIKE PEPTIDES ISOLATED FROM THE SPOTTED DOGFISH (SCYLIORHINUS-CANICULUS)

In contrast to most vertebrate species that possess one oxytocin-like hormone and one vasopressin-like hormone, a few groups, such as marsup ials or cartilaginous fishes, are endowed with two peptides of either or both types, suggesting possible gene duplications. We have now isol ated two oxytocin-like hormones from the pituitary of the spotted dogf ish Scyliorhinus caniculus (suborder Galeoidei). Microsequencing as we ll as chromatographic and pharmacological comparisons with synthetic p eptides show that these peptides are [Asn(4), Val(8)]oxytocin (asvatoc in) and [Phe(3), Asn(4), Val(8)]oxytocin (phasvatocin). Asvatocin and phasvatocin display oxytocic activity on rat uterus, about 80 and 5 mi lliunits per nmol, respectively, and virtually no presser activity on anesthetized rats. They occur in roughly equal molar amounts in the gl and; vasotocin is also present in a proportional amount that is lower by about a factor of 20. In addition to the duality, conservative amin o acid substitutions are observed in the two oxytocic peptides in posi tions 4 (Gln-4 --> Asn) and 8 (Leu-8 --> Val), when compared with oxyt ocin. Furthermore, replacement of the isoleucine residue found in posi tion 3 of all other oxytocin-like hormones by phenylalanine in phasvat ocin is exceptional; it determines a dramatic decrease of the oxytocic activity. Preservation of the C-terminal-amidated nonapeptide pattern in the 12 vertebrate neurohypophysial hormones known to date suggests that both precursors and processing enzymes have coevolved tightly. O n the other hand, whereas the great evolutionary stability of the matu re hormones (generally observed in vertebrates) suggests a strict mess enger-receptor coevolution, the exceptional diversity found in cartila ginous fishes (six oxytocin-like peptides identified out of eight know n) might be due to a looseness of selective constraints, perhaps in re lationship with their specific urea osmoregulation.