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Personne :
Sabourin, Thierry

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Sabourin

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Thierry

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Centre de recherche en rhumatologie et immunologie, Centre Hospitalier Universitaire de Québec, Université Laval

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ncf11848965

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  • PublicationAccès libre
    Vascular smooth muscle contractility assays for inflammatory and immunological mediators
    (Elsevier, 2010-09-08) Audet, Ritchie.; Deblois, Denis; Drapeau, Guy; Sabourin, Thierry; Bawolak, Marie-Thérèse; Koumbadinga, Gérémy Abdull; Fortin, Jean-Philippe.; Levesque, Luc; Marceau, François; Petitclerc, Éric; Morissette, Guillaume; Larrivée, Jean-François.; Godin, Denis; Gera, Lajos; Houle, Steeve.; Bouthillier, Johanne
    The blood vessels are one of the important target tissues for the mediators of inflammation and allergy; further cytokines affect them in a number of ways. We review the use of the isolated blood vessel mounted in organ baths as an important source of pharmacological information. While its use in the bioassay of vasoactive substances tends to be replaced with modern analytical techniques, contractility assays are effective to evaluate novel synthetic drugs, generating robust potency and selectivity data about agonists, partial agonists and competitive or insurmountable antagonists. For instance, the human umbilical vein has been used extensively to characterize ligands of the bradykinin B2 receptors. Isolated vascular segments are live tissues that are intensely reactive, notably with the regulated expression of gene products relevant for inflammation (e.g., the kinin B1 receptor and inducible nitric oxide synthase). Further, isolated vessels can be adapted as assays of unconventional proteins (cytokines such as interleukin-1, proteases of physiopathological importance, complement-derived anaphylatoxins and recombinant hemoglobin) and to the gene knockout technology. The well known cross-talks between different cell types, e.g., endothelium-muscle and nerve terminal-muscle, can be extended (smooth muscle cell interaction with resident or infiltrating leukocytes and tumor cells). Drug metabolism and distribution problems can be modeled in a useful manner using the organ bath technology, which, for all these reasons, opens a window on an intermediate level of complexity relative to cellular and molecular pharmacology on one hand, and in vivo studies on the other.
  • PublicationAccès libre
    Bradykinin receptors : agonists, antagonists, expression, signaling and adaptation to sustained stimulation
    (2013-12-01) Fortin, Sébastien; Sabourin, Thierry; Roy, Caroline; Bawolak, Marie-Thérèse; Koumbadinga, Gérémy Abdull; Fortin, Jean-Philippe.; Marceau, François; Morissette, Guillaume; Lodge, Robert; C. Gaudreault, René.; Houle, Steeve.; Charest-Morin, Xavier; Bouthillier, Johanne; Gera, Lajos
    Bradykinin-related peptides, the kinins, are blood-derived peptides that stimulate 2 G protein–coupled receptors, the B1 and B2 receptors (B1R, B2R). The pharmacologic and molecular identities of these 2 receptor subtypes will be succinctly reviewed, with emphasis on drug development, receptor expression, signaling, and adaptation to persistent stimulation. Peptide and nonpeptide antagonists and fluorescent ligands have been produced for each receptor. The B2R is widely and constitutively expressed in mammalian tissues, whereas the B1R is mostly inducible under the effect of cytokines during infection and immunopathology. Both receptor subtypes mediate the vascular aspects of inflammation (vasodilation, edema formation). On this basis, icatibant, a peptide antagonist of the B2R, is approved in the management of hereditary angioedema attacks. Other clinical applications are still elusive despite the maturity of the medicinal chemistry efforts applied to kinin receptors. While both receptor subtypes are mainly coupled to the Gq protein and related second messengers, the B2R is temporarily desensitized by a cycle of phosphorylation/endocytosis followed by recycling, whereas the nonphosphorylable B1R is relatively resistant to desensitization and translocated to caveolae on activation.