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Urotensin-II (U-II) is a vasoactive ‘somatostatin-like’ cyclic peptide which was originally isolated from fish spinal cords1,2, and which has recently been cloned from man3. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 (refs 4, 5) and expressed predominantly in cardiovascular tissue, which functions as a U-II receptor. Goby and human U-II bind to recombinant human GPR14 with high affinity, and the binding is functionally coupled to calcium mobilization. Human U-II is found within both vascular and cardiac tissue (including coronary atheroma) and effectively constricts isolated arteries from non-human primates. The potency of vasoconstriction of U-II is an order of magnitude greater than that of endothelin-1, making human U-II the most potent mammalian vasoconstrictor identified so far. In vivo, human U-II markedly increases total peripheral resistance in anaesthetized non-human primates, a response associated with profound cardiac contractile dysfunction. Furthermore, as U-II immunoreactivity is also found within central nervous system and endocrine tissues, it may have additional activities.

A series of potential affinity adsorbents for prephenate dehydratase were synthesized by coupling allosteric effectors to agarose with and without spacer arms. Only cationic ligands containing a hexamethylene spacer arm adsorbed the enzyme. Activity could be removed from aminohexyl- and glycyl-aminohexyl-agaroses with 0.5 M NaCl (with loss of activity), 0.4 M phosphate, or 140 mM hexanediamine, but was not removed from ala-aminohexyl-, phe-aminohexyl-, met-aminohexyl-, leu-aminohexyl-, or phenylpyruvyl-aminohexyl-agaroses or by Gly, Ala, Phe (inhibitor), Met or Leu (both activators). Urea (1.0 M), 1 mM phosphate, 50% glycerol in phosphate or prephenic acid (substrate) did not release enzymatic activity from any of the gels. The gel-bound enzyme was found to have enhanced activity comparable to that of the methionine-activated soluble enzyme. The site and mode of the enzyme immobilization are discussed in relation to the possible hydrophobic/ionic subunit-subunit interactions.

THE similarity of major biochemical pathways throughout the animal and plant kingdoms1 presumably reflects the ancient formation of the pathways in a common ancestral counterpart of modern cell types. The pathway previously known for L-tyrosine biosynthesis in both prokaryotie and eukaryotic microorganisms (Fig. 1a) involves a dehydrogenation-decarboxylation conversion of prephenate to 4-hydroxyphenylpyruvate followed by transamination in the presence of a suitable amino donor. Our data (Fig. 1b) demonstrate a reversed order of these two reactions in several species of blue–green algae (more appropriately designated bacteria (order Chrooeocales2)).