1833 QUINACRINE INHIBITS ARACHIDONIC-ACID INDUCED PULMONAR VASOCONSTRICTION

Abstract

Quinacrine (Q) has been described as an inhibitor of phospholipase A2 (PLA2). We have used quinacrine to inhibit arachidonic acid (AA)-induced pulmonary vasoconstriction in the isolated perfused rabbit lung. The lungs of five New Zealand White rabbits were isolated and pefused in a non-recirculating manner in situ with Krebs-Henseleit (KH) solution. AA was delivered into the inflow tubing at a dose of either 10 or 20 ug, depending on which dose produced a pulmonary vasopressor response (dPpa) of 10 torr or greater over baseline. The lungs were then perfused with Q-containing KH solution at a concentration of 0.1mM. (pH adjusted to 7.35-7.45) and rechallenged with arachidonic acid. Q was then washed out with plain KH solution for approximately 20 min and the lungs were bolused with a third dose of AA. Before Q perfusion dPpa=12.7±4.4 (mean±SD); after Q, dPpa=2.7±2; and after washout dPpa=10.2±6.5 torr. By 2-way ANOVA the effect of quinacrine was significant at P=0.002. By Least Significant Difference the pre-quinacrine and post-washout values for dPpa are not different. In our model, therefore, quinacrine is not a selective inhibitor of PLA2, and the inhibitory effect is reversible. These results suggest that quinacrine is an inhibitor of the smooth muscle contractile response, by acting as a calcium channel blocker or as a calmodulin inhibitor.