Kinin modulation of conventional outflow facility in the bovine eye.
The aim of this study was to investigate the effects of bradykinin on conventional outflow facility in relation to kinin effects on matrix metalloproteinase (MMP) secretion. Conventional outflow facility was measured in isolated bovine segments perfused at a constant pressure of 10 mmHg. Experiments were also performed in primary cultures of bovine trabecular meshwork cells to assess bradykinin effects on the secretion of MMP-9 assessed by western blot. Administration of bradykinin (10(-7) M) to perfused anterior segments produced a 50% increase in outflow facility above basal levels. The effect was slow to develop, requiring 100 min for a significant increase in facility and 4 h for the peak response to be observed. Pretreatment of anterior segments with the B(2) kinin receptor antagonist, HOE-140 (10(-6) M), or with the nonselective MMP inhibitor, GM6001 (10(-5) M) blocked the response to bradykinin (10(-7) M). Treatment of cultured trabecular meshwork cells with bradykinin (10(-7) M) for 120 min stimulated secretion of MMP-9 into the extracellular media, and this response was inhibited by HOE-140 (10(-6) M). These results demonstrate that bradykinin activates B(2) kinin receptors to increase conventional outflow in the perfused bovine eye and provide evidence that secretion and activation of MMPs within the conventional pathway may mediate the effect.
Webb
Jerry G
JG
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC 29725, USA. webbj@musc.edu
Husain
Shahid
S
Yates
Phillip W
PW
Crosson
Craig E
CE
D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects; D001082:Aqueous Humor / Q000378:metabolism*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065094:Bradykinin B2 Receptor Antagonists; D002417:Cattle; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology; D005123:Eye / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D013997:Time Factors
D065094:Bradykinin B2 Receptor Antagonists; D004151:Dipeptides; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D043782:Receptor, Bradykinin B2; C065679:icatibant; D020780:Matrix Metalloproteinase 9; D001920:Bradykinin