Vasoconstriction and bronchoconstriction induced by 2,5-di-(tert-butyl)1,4-benzohydroquinone, an endoplasmic reticular Ca2+-ATPase inhibitor, in isolated and perfused rat lung.
The microsomal Ca(2+)-ATPase inhibitor 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) induced bronchoconstriction and vasoconstriction in the isolated perfused and ventilated rat lung. These effects were accompanied by increased levels of thromboxane and prostacyclin in the effluent perfusate. The effect of tBuBHQ was inhibited by L-655,240, a thromboxane receptor antagonist, indicating thromboxane-A2-mediated bronchoconstriction and vasoconstriction. Accordingly, the cyclooxygenase inhibitor indomethacin largely blocked the effects of tBuBHQ. The involvement of a phospholipase in the generation of thromboxane A2(TXA2) was supported by dibucaine protection on tBuBHQ effects. The results from this study indicate that tBuBHQ, probably by inhibiting the microsomal Ca(2+)-ATPase, can trigger the arachidonic acid cascade leading to the formation of TXA2, which in turn causes bronchoconstriction and vasoconstriction in rat lung.
Atzori
L
L
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Bannenberg
G
G
Corriga
A M
AM
Ryrfeldt
A
A
Moldeus
P
P
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D006873:Hydroquinones / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D011651:Pulmonary Artery; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D013929:Thromboxane B2 / Q000096:biosynthesis; D014661:Vasoconstriction / Q000187:drug effects*
D006873:Hydroquinones; C019359:2,5-di-tert-butylhydroquinone; D013929:Thromboxane B2; D000252:Calcium-Transporting ATPases