Role of platelets in contraction of canine tracheal muscle elicited by PAF in vitro

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Abstract
To elucidate mechanisms of platelet-activating factor (PAF)-induced contraction, we studied the effect of PAF on 203 canine tracheal smooth muscle (TSM) strips from 45 dogs in vitro in the presence and absence of platelets. PAF (10-11 to 10-7) alone caused no contraction of TSM even in the presence of airway epithelium. In the presence of 2 .times. 105 platelets/.mu.1, PAF was an extremely potent contractile agonist (threshold 10-11 M). This response was inhibited by the PAF antagonist, CV-3988 (10-6 M), and reversed by the serotonin antagonist, methysergide (EC50 = 3.7 .+-. 0.79 .times. 10-9 M). Neither atropine nor chlorpheniramine (10-9 to 10-6 M) attenuated the response to PAF + platelets. In the presence of platelets, 10-7 M PAF caused an increase in perfusate concentration of serotonin from 0.93 .+-. 0.037 .times. 10-8 to 1.7 .+-. 0.046 .times. 10-8 M (P < 0.001). Tachyphylaxis, previously demonstrated to be irreversible, was shown to be a platelet-dependent phenomenon; contraction could be repeated in the same TSM after addition of fresh platelets. We demonstrate that PAF-induced contraction of canine TSM is caused by the release of cellular intermediates such as serotonin from platelets. We also demonstrate the site of PAF-induced tachyphylaxis in airway smooth muscle contraction.