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: M Szelke, D M Evans, D M Jones, L Fawcett, D Ashworth, H Olsson, R L Featherstone, M K Church
• Journal: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 27 Issue 8 Pg. 1943-7 (Aug 1994) ISSN: 0100-879X [Print] Brazil
• PMID: 7749385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aldehydes
• Ketones
• Peptides
• Ovalbumin
• Kallikreins
• Tissue Kallikreins

Topics

• Airway Resistance (drug effects)
• Aldehydes (pharmacology)
• Amino Acid Sequence
• Animals
• Bronchoalveolar Lavage Fluid
• Disease Models, Animal
• Guinea Pigs
• Hypersensitivity (physiopathology)
• Inflammation (physiopathology)
• Kallikreins (antagonists & inhibitors, metabolism)
• Ketones (pharmacology)
• Molecular Sequence Data
• Ovalbumin (administration & dosage)
• Peptides (pharmacology)
• Tissue Kallikreins