Involvement of Platelet Activating Factor in Respiratory Anaphylaxis, Demonstrated by Paf-Acether Inhibitor Bn 52021

Immediate anaphylactic bronchoconstriction induces airway hyperreactivity in anaesthetized guinea‐pigs

“…Indeed, quantitative changes in pulmonary fl-adrenoceptor number have been detected following repeated antigen-challenge in sensitized guinea-pigs (Gatto et al, 1987). Iso also fails to reverse completely airways obstruction in guineapigs rendered hyperreactive by prior exposure to Paf-acether (Barnes et al, 1987), which is a putative mediator of anaphylactic bronchospasm in this species (Braquet et al, 1985;Casals-Stenzel, 1987). There is however, no alteration in either ,Badrenoceptor number or function in pulmonary tissue excised from animals exposed to Paf-acether (Barnes et al, 1987).…”

Antagonism of Paf‐induced oedema formation in rabbit skin: a comparison of different antagonists

“…The degree of inhibition was incomplete, but substantial; responses to 10' mol and 10-10 mol Paf were reduced by 63 + 9% (P < 0.01) and 71 + 7% (P < 0.002) respectively (n = 5). In view of the unusual structure of BN 52021 (Braquet et al, 1985) Kadsurenone, L-652,731 and L-659,989…”

“…of Paf. Examples of Pafrelated compounds tested were CV-3988 (Terashita et al, 1983) and SRI 63-675 ; of natural products were BN-52021 (Braquet et al, 1985) and kadsurenone , and synthetic derivatives L-652,731 and L-659,989 (Ponpipom et al, 1988); of synthetic compounds was 48740 RP (Sedivy et al, 1985); and of pharmacological agents was WEB 2086 (CasalsStenzel et al, 1987 Zymosan-activated plasma (ZAP) was used as a source of C5a des Arg. Briefly, rabbit heparinized (10 u ml-1) plasma was incubated with zymosan (5mgml-1) for 30min at 370C followed by centrifugation, twice for 10min at 3000g, to remove the zymosan.…”

Effectiveness and tolerability of CV‐3988, a selective PAF antagonist, after intravenous administration to man.

“…Although PAF has been ascribed a potential role in various conditions such as inflammation (Bonnet et al, 1981;Pinckard et al, 1982), ulcerogenesis (Rosam et al, 1986), psoriasis (Mallet & Cunningham, 1985), allergy (Henson & Pinckard, 1977), asthma (Page et al, 1985;Braquet et al, 1985), endotoxin shock (Terashita et al, 1985), allergic vasculitis (Benveniste & Chignard, 1985), glomerulonephritis (Livio et al, 1986), thrombosis (Coeffier et al, 1986), disseminated intravascular coagulation (Imura et al, 1986) and even parturition (Ban et al, 1986), the precise role of PAF in physiologic/ pathophysiologic processes remains unclear. The introduction of inhibitors of the biosynthesis or of the receptor of PAF active in vivo could represent useful tools to extend our knowledge of the role of this mediator in health and disease.…”

“…Although several specific PAF-receptor antagonists, chemically related (Terahsita et al, 1983;Steiner et al, 1985) and unrelated to PAF (Braquet et al, 1985;Komecki et al, 1984;Hwang et al, 1985;Shen et al, 1985), have recently been reported, human pharmacology is very limited (Chung etal., 1987). Here we report that (RS)-2-methoxy-3-(octadecylcarbamoyloxy)-propyl 2-(3-thiazolio) ethylphosphate (CV-3988) (Terashita et al, 1983), when administered intravenously to human volunteers, inhibits PAF induced platelet aggregation ex vivo.…”