Platelet-activating Factor-mediated Contraction of Rabbit Lung Strips: Pharmacologic Modulation Giovanni Camussi, Giuseppe Montrucchio, Camillo Antro, Federico Bussolino, Ciro Tetta, and Giorgio Emanuelli. Abstract: Synthetic platelet-activating factor (PAF) (1-O-octadecyl-2-acetyl-sn-glyceryl-3- phosphorylcholine, AGEPC) has been shown to induce a slowly developing contraction of rabbit lung parenchymal strips in an isolated organ bath. The spasmogenic effect of AGEPC appeared to be mediated by specific receptors distinct from H l, H 2, cholinergic and CSa anaphylatoxin receptors. Prior exposure to AGEPC induced specific desensitization of lung parenchymal strips. Experiments with several pharmacological agents indicated that AGEPC- induced contraction was independent from cyclooxygenase, but was blocked when phosopholipase A 2 and lipoxygenase were inhibited and when the Ca ++ channels were antagonized. Corticosteroids exhibited an inhibitory effect specific for AGEPC. IntraceUular levels of cyclic AMP or cyclic GMP seemed to have a modulatory role in AGEPC-induced contraction of rabbit lung parenchymal strips. Key Words: Platelet-activating factor; Lung contraction INTRODUCTION The acetyl glyceryl ether of phosphatidylcholine (AGEPC) and its analogs are a new class of lipid chemical mediators of inflammation. The synthetic AGEPC has been shown to have a biological activity indistinguishable from that of native rabbit platelet-activating factor (PAF) (Benveniste et al., 1979; Demopoulos et al., 1979). Hanahan and coworkers (1980) have recently shown that PAF obtained from antigen-stimulated IgE-sensitized rabbit basophils comprises at least two structurally related polar phospholipids: 1-0-octadecyl (90%) and hexadecyl (10%)-2-acetyl-sn-glyceryl-3-phosphorylcholine. PAF is released in vivo in plasma during IgE anaphylaxis in the rabbit (Pinckard et al., 1979). The intravenous injection of synthetic AGEPC into normal rabbits reproduces the cardiovascu- lar and respiratory alterations associated with the anaphylactoid reaction (Halonen et al., 1980). Recent studies discriminate between the in vivo biological activities of AGEPC that occur as a consequence of platelet aggregation and/or secretion and those activities related to a Received May 25, 1982; revised and accepted January 27, 1983. From the Laboratorio di Immunopatologia, Cattedra di Nefrologia della Universit8 di Torino, Ospedale di S.Giovanni Battista e della Citt~ di Torino, e Cattedra di Patologia Medica "B" della Universit8 diTorino, Torino, Italy. Address requests for reprints to: Giovanni Camussi, Laboratorio di Immunopatologia, Cattedra di Nefrologia, Ospedale di S. Giovanni e della Citt8 di Torino. C. Polonia 14, 10126 Torino, Italy. © ElsevierScience PublishingCo., Inc., 1983 87 52 Vanderbilt Ave., New York, N.Y. lmmunopharmacology 6, 87-96 (1983) 0162-3109/83/$03.00