Thromboxane prostanoid receptor in human airway smooth muscle cells: A relevant role in proliferation

Valérie Capra, Aïda Habib, Maria Rosa Accomazzo, Saula Ravasi, Simona Citro, Sylviane Levy-Toledano, Simonetta Nicosia, G. Enrico Rovati

Research output: Contribution to journalArticle

Abstract

Thromboxane A2 has been implicated as a mediator of bronchial hyperresponsiveness in asthma. Modulating agents are currently marketed in Japan and under clinical evaluation in the US, but full characterization of the thromboxane A2 receptor and the signaling pathways that link it to the proliferative events taking place during airways structural remodeling has not been achieved. Here, we report that the presence of mRNA for both α and β isoforms of the thromboxane A2 receptor in smooth muscle cells from human bronchi correlates with protein expression evaluated by radioligand binding of the antagonist, SQ29,548 ([1S-[1α,2α(Z), 3α,4α]]-7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl] -7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic-acid) (Kd=3.4 nM±44%CV, coefficient of variation, Bmax=41 fmol/mg prot±38%CV). The receptor is functional, as the agonist, U46619 (9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic-acid), induced a concentration-dependent Ca2+ transient (EC 50=0.12 μM±27%CV). Furthermore, U46619 concentration dependently increased DNA synthesis and markedly potentiated the epidermal growth factor mitogenic effect. Both events were specifically inhibited by SQ29,548, independently from transactivation of the epidermal growth factor receptor and partially sensitive to pertussis toxin.

Original languageEnglish
Pages (from-to)149-159
Number of pages11
JournalEuropean Journal of Pharmacology
Volume474
Issue number2-3
DOIs
Publication statusPublished - Aug 8 2003

Keywords

  • Airway
  • Asthma
  • Human
  • Proliferation
  • Smooth muscle cell
  • Thromboxane A

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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  • Cite this

    Capra, V., Habib, A., Accomazzo, M. R., Ravasi, S., Citro, S., Levy-Toledano, S., Nicosia, S., & Rovati, G. E. (2003). Thromboxane prostanoid receptor in human airway smooth muscle cells: A relevant role in proliferation. European Journal of Pharmacology, 474(2-3), 149-159. https://doi.org/10.1016/S0014-2999(03)02014-4