Inhibitory effects of putative peptidic urotensin-II receptor antagonists on urotensin-II-induced contraction of cat isolated respiratory smooth muscle

Eur J Pharmacol. 2005 Jun 15;516(3):276-81. doi: 10.1016/j.ejphar.2005.04.043.

Abstract

Urotensin-II is purported to influence pulmonary function by modulating smooth muscle tone/growth. In the present study, Northern blot and reverse transcription polymerase chain reaction (RT-PCR) analysis indicated the presence of UT receptor mRNA in cat trachea, bronchi and lung parenchyma. Urotensin-II contracted cat isolated trachea and bronchi with similar potencies (pEC(50)s 8.61+/-0.07-8.81+/-0.10). Contractile efficacies ranged from 19+/-9% to 63+/-11% KCl in the primary and secondary bronchi. The peptidic UT receptor antagonists BIM-23127, SB-710411 and GSK248451 (7.18+/-0.12, 7.52+/-0.08 and 9.05+/-0.16 cat recombinant UT pK(i)s) inhibited urotensin-II-induced contraction of cat isolated trachea with pK(b)s 6.36+/-0.11, 6.74+/-0.07 and 9.27+/-0.12, respectively. As such, feline lung contains significant amounts of UT mRNA and this receptor appears to be functionally coupled to bronchoconstriction (the peptidic tool compound GSK248451 representing a sub-nanomolar inhibitor of such effects). These findings suggest that the cat represents a suitable species for future studies designed to assess the effects of the urotensin-II receptor on pulmonary (patho)physiology.

MeSH terms

  • Animals
  • Binding, Competitive
  • Blotting, Northern
  • Bronchi / drug effects
  • Bronchi / metabolism
  • Bronchi / physiology
  • Cats
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling
  • Humans
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Lung / drug effects
  • Lung / metabolism
  • Lung / physiology
  • Male
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacology*
  • Potassium Chloride / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radioligand Assay
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trachea / drug effects
  • Trachea / metabolism
  • Trachea / physiology
  • Urotensins / metabolism
  • Urotensins / pharmacology*

Substances

  • BIM 23127
  • GSK248451
  • Iodine Radioisotopes
  • Peptides, Cyclic
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • SB-710411
  • Urotensins
  • Potassium Chloride
  • urotensin II