PAF antagonists: different effects on platelets, neutrophils, guinea pig ileum and PAF-induced vasolidation in isolated rat lung |
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| Authors: | Norbert F Voelkel Shih-Wen Chang Kathy D Pfeffer Scott G Worthen Ivan F McMurtry Peter M Henson |
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| Institution: | 1. Cardiovascular Pulmonary Research Laboratory Denver, Colorado, USA;2. National Jewish Hospital, Denver, Colorado, USA;1. Department of Small Animal Medicine and Surgery, University of Veterinary Medicine, Hannover, Germany;2. Department of Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Hannover, Germany;1. Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover Foundation, Bünteweg 9, 30559 Hannover, Germany;2. Institute of Biochemistry, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany;3. Research Center for Emerging Infections and Zoonoses (RIZ), Bünteweg 17, 30559 Hannover, Germany;1. Veterinary Clinical Sciences, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia, Chile;2. Laboratory of Molecular Pharmacology, Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile;3. Applied Biochemistry Laboratory, Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile;4. School of Medicine, Medicine Faculty, Universidad Austral de Chile, Valdivia, Chile |
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| Abstract: | The effects of structurally different PAF receptor blockers were investigated in platelets, neutrophils, guinea pig ileum, rat isolated lung and rat isolated pulmonary artery. PAF caused serotonin release from platelets and a characteristic shape change and adhesion of neutrophils. The antagonists (CV 3988, alprazolam, 48740 RP and Merck-Sharp and Dohme L-652, 731) inhibited platelet serotonin release but not neutrophil shape change adhesion or lysosomal enzyme release. The antagonists in high concentrations (10−5 −10−4M) inhibited nonspecifically the PAF-induced (10−8M) guinea pig ileum contraction, but were ineffective at concentrations which inhibited platelet responses. In the rat lung the compounds, in high concentrations, partially inhibited the low dose PAF-induced pulmonary vasodilation and the high dose PAF induced pulmonary vasoconstriction and edema. Our data indicate that some platelet PAF antagonists may be ineffective in blocking the action of PAF on neutrophils and smooth muscle preparations and suggest either PAF-receptor independent actions of PAF or different classes of PAF receptors. |
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