title: Synthetic inhibitors of tissue kallikrein: effects in vivo in a model of allergic inflammation.
abstract: We have recently developed synthetic low molecular weight inhibitors of both tissue and plasma kallikreins. Several of these were evaluated in vivo in the ovalbumin-sensitised guinea pig for their ability to prevent the bronchoconstriction elicited by antigen challenge. The selective tissue kallikrein inhibitor CH-694 (but not the selective plasma kallikrein inhibitor CH-684) caused highly significant falls in airways resistance when it was administered at 10 mg/kg intraperitoneally 15 min before and 90 min after challenge. There was also a highly significant fall in the tissue kallikrein activity measured in broncho-alveolar lavage fluid. Inhibitors of tissue kallikrein may prove effective in the treatment of allergic inflammation in man.
authors.affiliation: Ferring Research Institute, University of Southampton Research Centre, Chilworth, UK.
authors.forename: M
authors.initials: M
authors.lastname: Szelke
authors.forename: D M
authors.initials: DM
authors.lastname: Evans
authors.forename: D M
authors.initials: DM
authors.lastname: Jones
authors.forename: L
authors.initials: L
authors.lastname: Fawcett
authors.forename: D
authors.initials: D
authors.lastname: Ashworth
authors.forename: H
authors.initials: H
authors.lastname: Olsson
authors.forename: R L
authors.initials: RL
authors.lastname: Featherstone
authors.forename: M K
authors.initials: MK
authors.lastname: Church
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000447:Aldehydes / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage; D010455:Peptides / Q000494:pharmacology; D020840:Tissue Kallikreins
chemical_list: D000447:Aldehydes; D007659:Ketones; D010455:Peptides; D010047:Ovalbumin; D007610:Kallikreins; D020840:Tissue Kallikreins