Skip to main content

Advertisement

Log in

A rat brain atlas of urotensin-II receptor expression and a review of central urotensin-II effects

  • REVIEW
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Urotensin-II (U-II) is an 11-amino acid cyclic peptide which exerts its actions through a Gq protein-coupled receptor, UT. Much of the research focus of U-II is as a peptide of the periphery, particularly cardiovascular. Despite this, U-II was originally identified as a neuropeptide, and its expression is broad throughout the central nervous system. This brief review article catalogs the known sites of expression of UT within the CNS in the form of a diagrammatic rat brain atlas. Furthermore, the functional consequences of UT activation within specific brain regions are discussed along with the likely actions of synthetic UT ligands. Areas of high, medium, and low expression include the arcuate, paraventricular, and pedunculopontine tegmental nuclei, respectively. In the arcuate and paraventricular nuclei, where expression is high and moderate, U-II produces a pressor/tachycardic response in the former and a weaker response in the latter. Based on the known pharmacology of UT ligands (and assuming density is the primary determinant of efficacy in this case), we predict a weak response in the arcuate nucleus and possible antagonism of endogenous U-II response in the paraventricular nucleus by a low-efficacy partial agonist. These predicted responses lend themselves to relatively simple experimental verification.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 77
Fig. 125
Fig. 162
Fig. 163
Fig. 164
Fig. 165
Fig. 166
Fig. 167
Fig. 169
Fig. 171
Fig. 173
Fig. 174
Fig. 176
Fig. 178

Similar content being viewed by others

References

  • Ames RS, Sarau HM et al (1999) Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 401(6750):282–286

    Article  CAS  PubMed  Google Scholar 

  • Ashton N (2006) Renal and vascular actions of urotensin II. Kidney Int 70(4):624–629

    Article  CAS  PubMed  Google Scholar 

  • Behm DJ, Stankus G et al (2006) The peptidic urotensin-II receptor ligand GSK248451 possesses less intrinsic activity than the low-efficacy partial agonists SB-710411 and urantide in native mammalian tissues and recombinant cell systems. Br J Pharmacol 148(2):173–190

    Article  CAS  PubMed  Google Scholar 

  • Bousette N, Giaid A (2006) Urotensin-II and cardiovascular diseases. Curr Hypertens Rep 8(6):479–483

    Article  CAS  PubMed  Google Scholar 

  • Brkovic A, Hattenberger A et al (2003) Functional and binding characterizations of urotensin II-related peptides in human and rat urotensin II-receptor assay. J Pharmacol Exp Ther 306(3):1200–1209

    Article  CAS  PubMed  Google Scholar 

  • Camarda V, Guerrini R et al (2002) A new ligand for the urotensin II receptor. Br J Pharmacol 137(3):311–314

    Article  CAS  PubMed  Google Scholar 

  • Camarda V, Spagnol M et al (2006) In vitro and in vivo pharmacological characterization of the novel UT receptor ligand [Pen5, DTrp7, Dab8]urotensin II(4–11) (UFP-803). Br J Pharmacol 147(1):92–100

    Article  CAS  PubMed  Google Scholar 

  • Carotenuto A, Grieco P et al (2004) Urotensin-II receptor peptide agonists. Med Res Rev 24(5):577–588

    Article  CAS  PubMed  Google Scholar 

  • Castel H, Diallo M et al (2006) Biochemical and functional characterization of high-affinity urotensin II receptors in rat cortical astrocytes. J Neurochem 99(2):582–595

    Article  CAS  PubMed  Google Scholar 

  • Clark SD, Nothacker HP et al (2001) The urotensin II receptor is expressed in the cholinergic mesopontine tegmentum of the rat. Brain Res 923(1–2):120–127

    Article  CAS  PubMed  Google Scholar 

  • Clozel M, Binkert C et al (2004) Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin system. J Pharmacol Exp Ther 311(1):204–212

    Article  CAS  PubMed  Google Scholar 

  • Coulouarn Y, Lihrmann I et al (1998) Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord. Proc Natl Acad Sci USA 95(26):15803–15808

    Article  CAS  PubMed  Google Scholar 

  • Do-Rego JC, Chatenet D et al (2005) Behavioral effects of urotensin-II centrally administered in mice. Psychopharmacology (Berl) 183(1):103–117

    Article  CAS  Google Scholar 

  • Do Rego JC, Leprince J et al (2008) Behavioral actions of urotensin-II. Peptides 29(5):838–844

    Article  CAS  PubMed  Google Scholar 

  • Dubessy C, Cartier D et al (2008) Characterization of urotensin II, distribution of urotensin II, urotensin II-related peptide and UT receptor mRNAs in mouse: evidence of urotensin II at the neuromuscular junction. J Neurochem 107(2):361–374

    Article  CAS  PubMed  Google Scholar 

  • Flohr S, Kurz M et al (2002) Identification of nonpeptidic urotensin II receptor antagonists by virtual screening based on a pharmacophore model derived from structure-activity relationships and nuclear magnetic resonance studies on urotensin II. J Med Chem 45(9):1799–1805

    Article  CAS  PubMed  Google Scholar 

  • Gartlon J, Parker F et al (2001) Central effects of urotensin-II following ICV administration in rats. Psychopharmacology (Berl) 155(4):426–433

    Article  CAS  Google Scholar 

  • Grieco P, Carotenuto A et al (2002) A new, potent urotensin II receptor peptide agonist containing a Pen residue at the disulfide bridge. J Med Chem 45(20):4391–4394

    Article  CAS  PubMed  Google Scholar 

  • Grieco P, Carotenuto A et al (2005) Urotensin-II receptor ligands. From agonist to antagonist activity. J Med Chem 48(23):7290–7297

    Article  CAS  PubMed  Google Scholar 

  • Huitron-Resendiz S, Kristensen MP et al (2005) Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons. J Neurosci 25(23):5465–5474

    Article  CAS  PubMed  Google Scholar 

  • Jegou S, Cartier D et al (2006) Localization of the urotensin II receptor in the rat central nervous system. J Comp Neurol 495(1):21–36

    Article  CAS  PubMed  Google Scholar 

  • Kawaguchi Y, Ono T et al (2009) The effects of benzodiazepines on urotensin II-stimulated norepinephrine release from rat cerebrocortical slices. Anesth Analg 108(4):1177–1181

    Article  CAS  PubMed  Google Scholar 

  • Le Mevel JC, Lancien F et al (2008) Central and peripheral cardiovascular, ventilatory, and motor effects of trout urotensin-II in the trout. Peptides 29(5):830–837

    Article  PubMed  Google Scholar 

  • Leprince J, Chatenet D et al (2008) Structure-activity relationships of urotensin II and URP. Peptides 29(5):658–673

    Article  CAS  PubMed  Google Scholar 

  • Lin Y, Tsuchihashi T et al (2003a) Central cardiovascular action of urotensin II in conscious rats. J Hypertens 21(1):159–165

    Article  CAS  PubMed  Google Scholar 

  • Lin Y, Tsuchihashi T et al (2003b) Central cardiovascular action of urotensin II in spontaneously hypertensive rats. Hypertens Res 26(10):839–845

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Zou CJ et al (2002) Cardiovascular effects of urotensin II in different brain areas. Peptides 23(9):1631–1635

    Article  CAS  PubMed  Google Scholar 

  • Maguire JJ, Kuc RE et al (2000) Orphan-receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin-1. Br J Pharmacol 131(3):441–446

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto Y, Abe M et al (2004) Intracerebroventricular administration of urotensin II promotes anxiogenic-like behaviors in rodents. Neurosci Lett 358(2):99–102

    Article  CAS  PubMed  Google Scholar 

  • McDonald J, Batuwangala M et al (2007) Role of urotensin II and its receptor in health and disease. J Anesth 21(3):378–389

    Article  PubMed  Google Scholar 

  • Ono T, Kawaguchi Y et al (2008) Urotensin II evokes neurotransmitter release from rat cerebrocortical slices. Neurosci Lett 440(3):275–279

    Article  CAS  PubMed  Google Scholar 

  • Papadopoulos P, Bousette N et al (2008) Urotensin-II and cardiovascular remodeling. Peptides 29(5):764–769

    Article  CAS  PubMed  Google Scholar 

  • Patacchini R, Santicioli P et al (2003) Urantide: an ultrapotent urotensin II antagonist peptide in the rat aorta. Br J Pharmacol 140(7):1155–1158

    Article  CAS  PubMed  Google Scholar 

  • Pearson D, Shively JE et al (1980) Urotensin II: a somatostatin-like peptide in the caudal neurosecretory system of fishes. Proc Natl Acad Sci USA 77(8):5021–5024

    Article  CAS  PubMed  Google Scholar 

  • Richards AM, Charles C (2004) Urotensin II in the cardiovascular system. Peptides 25(10):1795–1802

    Article  CAS  PubMed  Google Scholar 

  • Russell FD (2004) Emerging roles of urotensin-II in cardiovascular disease. Pharmacol Ther 103(3):223–243

    Article  CAS  PubMed  Google Scholar 

  • Sugo T, Murakami Y et al (2003) Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain. Biochem Biophys Res Commun 310(3):860–868

    Article  CAS  PubMed  Google Scholar 

  • Tal M, Ammar DA et al (1995) A novel putative neuropeptide receptor expressed in neural tissue, including sensory epithelia. Biochem Biophys Res Commun 209(2):752–759

    Article  CAS  PubMed  Google Scholar 

  • Totsune K, Takahashi K et al (2001) Role of urotensin II in patients on dialysis. Lancet 358(9284):810–811

    Article  CAS  PubMed  Google Scholar 

  • Vaudry H, Do Rego JC et al (2010) Urotensin II, from fish to human. Ann N Y Acad Sci (in press)

  • Watson AM, Lambert GW et al (2003) Urotensin II acts centrally to increase epinephrine and ACTH release and cause potent inotropic and chronotropic actions. Hypertension 42(3):373–379

    Article  CAS  PubMed  Google Scholar 

  • Watson AM, May CN (2004) Urotensin II, a novel peptide in central and peripheral cardiovascular control. Peptides 25(10):1759–1766

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

BDH is a British Heart Foundation-funded Ph.D. student. We wish to acknowledge the exhaustive work of (Jegou et al. 2006) on which this brain atlas is largely based and thank the corresponding author, Professor H. Vaudry, for critically reviewing our manuscript. Finally, a simple PubMed search for “urotensin II” yields approximately 550 hits; we therefore wish to apologize to those authors whose work we were unable to cite due to limitations of space.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David G. Lambert.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hunt, B.D., Ng, L.L. & Lambert, D.G. A rat brain atlas of urotensin-II receptor expression and a review of central urotensin-II effects. Naunyn-Schmied Arch Pharmacol 382, 1–31 (2010). https://doi.org/10.1007/s00210-010-0503-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-010-0503-z

Keywords

Navigation