Elsevier

Peptides

Volume 29, Issue 5, May 2008, Pages 651-657
Peptides

“Liberation” of urotensin II from the teleost urophysis: An historical overview

https://doi.org/10.1016/j.peptides.2007.04.021Get rights and content

Abstract

During the past 20 years, urotensin II (UII) has progressed from being a peptide synthesized only in the urophysis of the caudal neurosecretory system of teleost fish to being considered an important physiological regulator in mammals with implications for the pathogenesis of a range of human cardiovascular and renal diseases. The “liberation” of UII from the urophysis was a gradual process and involved the sequential realization that (a) UII is present not only in the urophysis but also in the central nervous systems (CNS) of teleosts, (b) UII peptides, similar in structure to the urophysial peptides, are present in the diffuse caudal neurosecretory systems and/or CNS of species less evolutionarily advanced than teleosts, including Agnatha, thereby showing that UII is a phylogenetically ancient peptide, (c) UII is present in the brain and spinal cord of a tetrapod, the green frog Rana ridibunda, and (d) the UII gene and its specific receptor (GPR14/UT) are expressed in the CNS and certain peripheral tissues of mammals, including the human. The discovery that the genomes of mammals contain an additional gene encoding a UII-related peptide (URP) and the availability of highly effective peptide and non-peptide antagonists to investigate the role of UII in human physiology and pathophysiology ensure that the peptide will remain “center stage” for several years to come.

Introduction

As readers of this volume will become aware, urotensin II (UII) is now recognized as an important regulator of several physiological processes in mammals with involvement in the pathophysiology of a range of human cardiovascular and renal diseases. Twenty years ago, in marked contrast, UII was regarded as a “neurohormone from fish tails” [7], [9] and, as such, belonged exclusively to the province of the comparative endocrinologist. The urophysis, a neurohemal organ located at the caudal terminus of the spinal cord, was considered to be the only site of synthesis of UII and, as the urophysis is found only in teleost fish, it was tacitly assumed that UII occurred only in this class of vertebrate. Clearly, much has happened in a relatively short period of time to change our view of UII and this historical review attempts to chart the “liberation” of the peptide from its confinement in the teleost urophysis.

Our realization that UII is not just a chemical curiosity, particular to one tissue in one group of organisms, but a neurohormonal regulator in all classes of vertebrate was accomplished in a progressive manner. Initially, it was demonstrated that UII is present not only in the urophysis but also in the central nervous systems (CNS) of teleost fish [69], [74], [75]. Subsequently, UII peptides, similar in structure to the urophysial peptides, were shown to be present in the diffuse caudal neurosecretory systems and/or CNS of species less evolutionarily advanced than teleosts, including elasmobranchs [19], [69], chondrosteans [48], [70] and Agnatha [70]. This showed that the gene encoding UII is phylogenetically ancient and had clearly arisen before the emergence of teleosts. The first demonstration that the UII gene is expressed in the tissues of a tetrapod was the isolation of the peptide from an extract of the brain of the amphibian, the green frog Rana ridibunda [20]. This result led to the identification of the UII gene in the genomes of the human [22], rat [21], mouse [21], and pig [50] and the recognition that UII was the cognate ligand for the GPR14 orphan G-protein-coupled receptor [1], [42], [50], [52], thereby setting the stage for the on-going investigation of the role of UII in human health and disease.

The discovery that the genomes of mammals contain an additional gene that is evolutionarily related to the UII gene and encodes a urotensin-related peptide (URP) [64], and the availability of highly effective peptide [61] and non-peptide [25] antagonists to investigate the role of UII in human physiology and pathophysiology have opened exciting new chapters in what was once restrictively described as “urophysiology”.

Section snippets

The caudal neurosecretory system of teleosts

The history of the caudal neurosecretory system dates back to 1827 with the first recognition by Weber [71] of the anatomical structure in the carp that was subsequently referred to as the urophysis. The organ, present only in teleosts, is a macroscopically visible enlargement of the spinal cord in the last vertebral segment that is said to be most prominent in actively swimming species [34]. In work not generally accepted at the time but subsequently recognized as the first formulation of the

The caudal neurosecretory system of non-teleost fish

The existence of a caudal neurosecretory system in elasmobranchs has been established morphologically and its histological organization has been described for the dogfishes, Squalus acanthias [27], [57], Scyliorhinus torzame and Triakis scyllia [59] and for the rays, Dasyatis akajei [59] and Raia radiata [27]. In these species, nerve terminals are not concentrated into a compact urophysis but large caudal neurosecretory neurons project onto diffuse neurohemal areas on the ventral surface of the

Isolation of urotensin II from frog brain

The existence of high affinity specific binding sites (putative receptors) for 125I-labeled goby UII on membranes prepared from the major rat arteries [36] and the ability of the peptide to relax mouse anococcygeus muscle [29], to produce sustained hypotension in the anesthetized rat [30], [31] and to elicit complex contractile and relaxant effects on rat aorta [28] suggested the possibility that UII, or a related peptide, may be produced in mammalian tissues. However, the first unequivocal

Concluding comment

In 1985, in an article entitled ‘The elusive urophysis’, Bern wrote “Advances in the field have been impeded by the paucity of investigators, not by the paucity of stimulating questions” [6]. With the identification of UII and its receptor in the human and the recognition that the peptide may play a pivotal role in the pathogenesis of several human diseases, there is now no shortage of investigators to address the question of the physiological role of UII in the human. Nevertheless, the

Acknowledgments

The author thanks Richard Balment, Nicolas Chartrel, Neil Hazon, Jean-Claude LeMevel, Finbarr O’Harte, Ken Olson, Hervé Tostivint, Hubert Vaudry, David Waugh, and Kenji Yano for enjoyable and productive collaborations relating to UII over nearly 20 years.

References (76)

  • Y. Honma et al.

    Studies on Japanese chars of the genus Salvelinus. IV. The caudal neurosecretory system of the Nikko-iwana, Salvelinus leucomaenis pluvius (Hilgendorf)

    Gen Comp Endocrinol

    (1967)
  • H. Itoh et al.

    Functional receptors for fish neuropeptide urotensin II in major rat tail arteries

    Eur J Pharmacol

    (1988)
  • F. Lacanilao

    The urophysial hydroosmotic factor of fishes. II. Chromatographic and pharmacologic indication of similarity to arginine vasopressin

    Gen Comp Endocrinol

    (1972)
  • F. Lancien et al.

    Central effects of native urotensin II on motor activity, ventilatory movements, and heart rate in the trout Oncorhynchus mykiss

    Brain Res

    (2004)
  • K. Lederis

    Teleost urophysis I. Bioassay of an active urophysial principle on the isolated urinary bladder of the rainbow trout, Salmo gairdnerii

    Gen Comp Endocrinol

    (1970)
  • Q. Liu et al.

    Identification of urotensin II as the endogenous ligand for the orphan G-protein-coupled receptor GPR14

    Biochem Biophys Res Commun

    (1999)
  • C.A. Loretz et al.

    Stimulation of sodium transport across the teleost urinary bladder by urotensin II

    Gen Comp Endocrinol

    (1981)
  • D. McMaster et al.

    Isolation and amino acid sequence of urotensin II from the sturgeon Acipenser ruthenus

    Gen Comp Endocrinol

    (1992)
  • D. McMaster et al.

    Isolation and amino acid sequence of two urotensin II peptides from Catostomus commersoni urophyses

    Peptides

    (1983)
  • M. Mori et al.

    Urotensin II is the endogenous ligand of a G-protein-coupled orphan receptor, SENR (GPR14)

    Biochem Biophys Res Commun

    (1999)
  • D. Onan et al.

    Urotensin II: the old kid in town

    Trends Endocrinol Metab

    (2004)
  • T. Sugo et al.

    Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain

    Biochem Biophys Res Commun

    (2003)
  • D. Waugh et al.

    Purification and characterization of urotensin II from the brain of a teleost (trout, Oncorhynchus mykiss) and an elasmobranch (skate, Raja rhina)

    Gen Comp Endocrinol

    (1993)
  • D. Waugh et al.

    Urotensin II from the river lamprey (Lampetra fluviatilis), the sea lamprey (Petromyzon marinus), and the paddlefish (Polyodon spathula)

    Gen Comp Endocrinol

    (1995)
  • K. Yano et al.

    Cardiovascular actions of frog urotensin II in the frog, Rana catesbeiana

    Gen Comp Endocrinol

    (1995)
  • K. Yano et al.

    Spasmogenic actions of frog urotensin II on the bladder and ileum of the frog, Rana catesbeiana

    Gen Comp Endocrinol

    (1994)
  • C.R. Yulis et al.

    Occurrence of an anterior spinal, cerebrospinal fluid-contacting, urotensin II neuronal system in various fish species

    Gen Comp Endocrinol

    (1988)
  • R.S. Ames et al.

    Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14

    Nature

    (1999)
  • M.A. Belenky et al.

    Immunocytochemical investigation of localization of urotensins I and II in the central nervous system of Acipenseridae

    Tsitologiya

    (1989)
  • A. Berlind

    Teleost caudal neurosecretory system: sperm duct contraction induced by urophysial material

    J Endocrinol

    (1972)
  • H.A. Bern

    The elusive urophysis—twenty-five years in pursuit of caudal neurohormones

    Am Zool

    (1985)
  • H.A. Bern

    The caudal neurosecretory system: quest and bequest

    (1990)
  • H.A. Bern et al.

    A reference preparation for the study of active substances in the caudal neurosecretory system of teleosts

    J Endocrinol

    (1969)
  • D.R. Brady

    Caudal neurosecretory system of the paddlefish, Poyodon spathula

    Zool Anz Jena

    (1984)
  • N. Chartrel et al.

    Strategy for identification of new neuropeptides

    C R Seances Soc Biol Fil

    (1998)
  • N. Chartrel et al.

    Urotensin II in the central nervous system of the frog Rana ridibunda: immunohistochemical localization and biochemical characterization

    J Comp Neurol

    (1996)
  • N. Chartrel et al.

    Biochemical characterization and immunohistochemical localization of urotensin II in the human brainstem and spinal cord

    J Neurochem

    (2004)
  • C. Cioni et al.

    Development of the caudal neurosecretory system of the nile tilapia Oreochromis niloticus: an immunohistochemical and electron microscopic study

    J Morphol

    (2000)
  • Cited by (21)

    • Urotensin II-related peptide (Urp) is expressed in motoneurons in zebrafish, but is dispensable for locomotion in larva

      2021, Peptides
      Citation Excerpt :

      Urotensin 2 (Uts2) is a cyclic neuropeptide that was first isolated from the urophysis of the teleost fish goby Gillichthys mirabilis [1] and subsequently identified in most vertebrate species [2].

    • Study of the association between Urotensin 2 (p.T21M and p.S89N) variants and breast cancer in Egyptian patients

      2020, Gene Reports
      Citation Excerpt :

      It is a 12 amino acid cyclic peptide that is produced as a result of the cleavage of preproprotein (pre-pro-UTS2). There are two splice variants of the pre-pro-UTS2, one with 124 amino acids and the second with 139 amino acids (Coulouarn et al., 1998; Conlon, 2008). UTS2 mediates its action by binding to urotensin receptors (UTRs), which were formerly named GPR14 (G-Protein-Coupled Receptor-14) (Liu et al., 1999).

    • Urotensin II alters vascular reactivity in animals subjected to volume overload

      2010, Peptides
      Citation Excerpt :

      UTII binding causes prolonged activation of the ERK1/2 MAPK pathway in isolated cardiomyocytes [34], while also causing an increase in intracellular Ca2+ mobilization [1,30]. Generally, it has been shown that both circulating UTII and its receptor expression are widely distributed throughout the body at low levels [5]. However, both the receptor and ligand appear to be up-regulated in the presence of cardiovascular pathologies, including congestive heart failure [7,10].

    • Urotensin I-CRF-Urocortins: A mermaid's tail

      2009, General and Comparative Endocrinology
    • Editorial

      2008, Peptides
    View all citing articles on Scopus
    View full text