Thiol modification in H2O2- and thromboxane-induced vaso- and bronchoconstriction in rat perfused lung.
Hydrogen peroxide (H2O2), arachidonic acid (AA), and U-44069, a thromboxane analogue, all induced vaso- and bronchoconstriction in the isolated perfused rat lung. The role of protein sulfhydryl modifications in these processes was investigated. The thiol oxidizing agent diamide inhibited both vaso- and bronchoconstriction induced by H2O2, AA, or U-44069. Diamide had only a marginal effect on glutathione and protein thiol levels and no effect on lung mechanics. The diamide inhibition was reversible, and H2O2-induced vaso- and bronchoconstriction was almost maximal after 10 min of perfusion with buffer. The recovery was more rapid if dithiothreitol, a thiol reducing agent, was used in the buffer. H2O2- and AA-induced vaso- and bronchoconstriction is caused by thromboxane release. Diamide did not influence H2O2- or AA-dependent thromboxane formation, indicating that neither AA release nor AA metabolism to thromboxane is sensitive to thiol oxidation. Thus our results indicate that the site of diamide-induced thiol oxidation is the thromboxane receptor or its signal transduction.
Atzori
L
L
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Olafsdóttir
K
K
Corriga
A M
AM
Bannenberg
G
G
Ryrfeldt
A
A
Moldéus
P
P
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D003958:Diamide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D011654:Pulmonary Edema / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D007211:Indoles; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D013931:Thromboxanes; C052517:L 655240; D003958:Diamide; D016718:Arachidonic Acid; D012701:Serotonin; D013929:Thromboxane B2; D006861:Hydrogen Peroxide; D001920:Bradykinin; D004229:Dithiothreitol