Effects of Pasteurella haemolytica culture supernate on bovine tracheal smooth muscle.

Pasteurella haemolytica leukotoxin is a ruminant specific leukotoxin that has been implicated in the pathogenesis of shipping fever in cattle. The present study was undertaken to determine the effect of this toxin on bovine airway smooth muscle. In vitro, the addition of culture supernate containing leukotoxin to bovine tracheal smooth muscle resulted in contraction of 55% of the muscle strips tested. Maximum responses were reached rapidly during cumulative additions of this material. In 95% of the muscle strips that responded, maximum responses were obtained after the addition of one or two cumulative doses. Repeated additions of culture supernate resulted in decreased responsiveness. Since responsiveness to other agonists was not affected, these results suggest the development of a condition similar to tachyphylaxis. The contractions were inhibited by antihistamines. Diphenhydramine, at a concentration of 10(-6) M (dose-ratio 7), and mepyramine, at a concentration of 2 x 10(-7) M (dose-ratio 56), blocked the contractions by 84% and 100% respectively. In addition, the contractions were blocked by the muscarinic antagonist atropine, but this inhibition was much weaker (46%) and was present at high concentrations only. Inhibition of the contractions by H1 receptor antagonists suggests that the contractions are mediated via H1 receptors. Since the dose-response relationship is not typical of a drug-receptor interaction, it appears unlikely that the leukotoxin is a direct agonist of H1 receptors. It is proposed that an indirect mechanism of action involving the release of histamine by tissue mast cells is responsible for the leukotoxin-induced contractions.