EFFECTS OF LIPOSOME-ENTRAPPED PLATELET-ACTIVATING-FACTOR IN THE ISOLATED RAT TRACHEA

The effects of platelet-activating factor (PAF, alkyl-2-acetyl-sn-glyc ero-3-phosphocholine)-filled liposomes upon rat tracheal rings in vitr o were examined. The capture of liposomes by the smooth muscle cells o f the isolated tracheal rings as well as the release of their content into the cytoplasm was shown by using Evans blue (5 x 10(-4) M)-loaded liposomes. Administration of PAF (10(-3) M)-filled liposomes contract ed the preparations, in contrast with extracellular administration of PAF and control liposomes, which had no effect. Administration during the plateau or pretreatment with liposomes containing BN 52021 ymethan o-1H,6aH-cyclopenta[c]furo(2,3-b)furo[3',2' :3,4]cyclopental [1,2-d]fu ran-5,9,12(4H)-trione) ((10(-3) M, a selective PAF receptor antagonist ) or heparin (5 x 10(-5) M) blocked this contraction. BN 52021 and hep arin, not entrapped in liposomes, had no such effect. Our data suggest an intervention of PAF in the mechanisms of contraction of tracheal s mooth muscle, involving a direct or indirect intervention (intracellul ar receptors for PAF cannot be excluded). At the same time, the rat tr achea contraction induced by PAF-loaded liposomes could be linked to t he PtdIns(1,4,5)P-3-dependent Ca2+ channels from the endoplasmic retic ulum and/or to the interaction with G proteins, as shown by the blocki ng effects of heparin-containing liposomes.