Synthetic inhibitors of tissue kallikrein: effects in vivo in a model of allergic inflammation.
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.
Szelke
M
M
Ferring Research Institute, University of Southampton Research Centre, Chilworth, UK.
Evans
D M
DM
Jones
D M
DM
Fawcett
L
L
Ashworth
D
D
Olsson
H
H
Featherstone
R L
RL
Church
M K
MK
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
D000447:Aldehydes; D007659:Ketones; D010455:Peptides; D010047:Ovalbumin; D007610:Kallikreins; D020840:Tissue Kallikreins