Effects of liposome-entrapped platelet-activating factor in the isolated rat trachea

• Published in: European journal of pharmacology 1995-07, Vol.281 (1), p.89-92
• Main Authors: Costuleanu, Marcel, Brailoiu, Eugen, Filipeanu, Catalin M., Baltatu, Ovidiu, Slatineanu, Sebastian, Saila, Liliana, Nechifor, Mihai, Branisteanu, Dimitrie D.
• Format: Article
• Language: English
• Subjects: Air breathing; Animals; Biological and medical sciences; Cytoplasm - metabolism; Diterpenes; Drug Carriers; Epithelium - physiology; Evans Blue - administration & dosage; Evans Blue - pharmacokinetics; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - pharmacology; Fundamental and applied biological sciences. Psychology; Ginkgolides; Heparin - administration & dosage; Heparin - pharmacology; In Vitro Techniques; Kinetics; Lactones - administration & dosage; Lactones - pharmacokinetics; Liposome; Liposomes; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Muscle, Smooth - physiology; PAF (platelet-activating factor); Platelet Activating Factor - administration & dosage; Platelet Activating Factor - pharmacokinetics; Rats; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics; Smooth muscle, trachea; Trachea - drug effects; Trachea - metabolism; Vertebrates: respiratory system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00276-Q

The effects of platelet-activating factor (PAF, 1- O-alkyl-2-acetyl- sn-glycero-3-phosphocholine)-filled liposomes upon rat tracheal rings in vitro were examined. The capture of liposomes by the smooth muscle cells of the isolated tracheal rings as well as the release of their content into the cytoplasm was shown by using Evans blue (5 × 10 −4 M)-loaded liposomes. Administration of PAF (10 −3 M)-filled liposomes contracted 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 (3- t-butylhexahydro-4,7b-trihydroxy-8-methyl-9 H-1,7 a-epoxymethano-1 H,6 aH-cyclopenta[ c]furo(2,3- b)furo[3′,2′:3,4]cyclope ((10 −3 M, a selective PAF receptor antagonist) or heparin (5 × 10 −5 M) blocked this contraction. BN 52021 and heparin, not entrapped in liposomes, had no such effect. Our data suggest an intervention of PAF in the mechanisms of contraction of tracheal smooth muscle, involving a direct or indirect intervention (intracellular receptors for PAF cannot be excluded). At the same time, the rat trachea contraction induced by PAF-loaded liposomes could be linked to the PtdIns(1,4,5)P 3-dependent Ca 2+ channels from the endoplasmic reticulum and/or to the interaction with G proteins, as shown by the blocking effects of heparin-containing liposomes.