title: Thromboxane prostanoid receptor in human airway smooth muscle cells: a relevant role in proliferation.
abstract: Thromboxane A(2) 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 A(2) 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 alpha and beta isoforms of the thromboxane A(2) receptor in smooth muscle cells from human bronchi correlates with protein expression evaluated by radioligand binding of the antagonist, SQ29,548 ([1S-[1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic-acid) (K(d)=3.4 nM+/-44%CV, coefficient of variation, B(max)=41 fmol/mg prot+/-38%CV). The receptor is functional, as the agonist, U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy-prosta-5Z,13E-dien-1-oic-acid), induced a concentration-dependent Ca(2+) transient (EC(50)=0.12 microM+/-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.
authors.affiliation: Institut Féderatif de Recherche Circulation-Lariboisière, Hôpital Lariboisière, 75010 Paris, France. Valerie.Capra@unimi.it
authors.forename: Valérie
authors.initials: V
authors.lastname: Capra
authors.forename: Aïda
authors.initials: A
authors.lastname: Habib
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Accomazzo
authors.forename: Saula
authors.initials: S
authors.lastname: Ravasi
authors.forename: Simona
authors.initials: S
authors.lastname: Citro
authors.forename: Sylviane
authors.initials: S
authors.lastname: Levy-Toledano
authors.forename: Simonetta
authors.initials: S
authors.lastname: Nicosia
authors.forename: G Enrico
authors.initials: GE
authors.lastname: Rovati
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000502:physiology*
chemical_list: D044244:Receptors, Thromboxane A2, Prostaglandin H2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid