Role of platelets in contraction of canine tracheal muscle elicited by PAF in vitro.
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) M) alone caused no contraction of TSM even in the presence of airway epithelium. In the presence of 2 x 10(5) platelets/microliter, 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 x 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 x 10(-8) to 1.7 +/- 0.046 x 10(-8) M (P less than 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.
Popovich
K J
KJ
Section of Pulmonary and Critical Care Medicine, University of Chicago, Illinois 60637.
Sheldon
G
G
Mack
M
M
Munoz
N M
NM
Denberg
P
P
Blake
J
J
White
S R
SR
Leff
A R
AR
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D004285:Dogs; D005260:Female; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology*; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012701:Serotonin / Q000032:analysis; D013618:Tachyphylaxis; D014132:Trachea / Q000502:physiology*
D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D012701:Serotonin; D001285:Atropine; C037913:CV 3988; D008784:Methysergide