“Liberation” of urotensin II from the teleost urophysis: An historical overview
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.
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Urotensin II-related peptide (Urp) is expressed in motoneurons in zebrafish, but is dispensable for locomotion in larva
2021, PeptidesCitation 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 ReportsCitation 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, PeptidesCitation 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].
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