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

38 Citations (Scopus)

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

Fingerprint

Prostaglandin H2 Receptors Thromboxane A2
Thromboxane Receptors
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Prostaglandins
Smooth Muscle Myocytes
RNA Isoforms
Airway Remodeling
Thromboxane A2
Pertussis Toxin
Bronchi
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Transcriptional Activation
Japan
Asthma
Acids
DNA
Proteins
SQ 29548

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Thromboxane prostanoid receptor in human airway smooth muscle cells : A relevant role in proliferation. / Capra, Valérie; Habib, Aïda; Accomazzo, Maria Rosa; Ravasi, Saula; Citro, Simona; Levy-Toledano, Sylviane; Nicosia, Simonetta; Rovati, G. Enrico.

In: European Journal of Pharmacology, Vol. 474, No. 2-3, 08.08.2003, p. 149-159.

Research output: Contribution to journalArticle

Capra, V, Habib, A, Accomazzo, MR, Ravasi, S, Citro, S, Levy-Toledano, S, Nicosia, S & Rovati, GE 2003, 'Thromboxane prostanoid receptor in human airway smooth muscle cells: A relevant role in proliferation', European Journal of Pharmacology, vol. 474, no. 2-3, pp. 149-159. https://doi.org/10.1016/S0014-2999(03)02014-4
Capra, Valérie ; Habib, Aïda ; Accomazzo, Maria Rosa ; Ravasi, Saula ; Citro, Simona ; Levy-Toledano, Sylviane ; Nicosia, Simonetta ; Rovati, G. Enrico. / Thromboxane prostanoid receptor in human airway smooth muscle cells : A relevant role in proliferation. In: European Journal of Pharmacology. 2003 ; Vol. 474, No. 2-3. pp. 149-159.
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