EFFECTS OF THIAZINAMIUM CHLORIDE AND OTHER ANTIHISTAMINES ON PHOSPHATIDYLCHOLINE SECRETION IN RAT TYPE-II PNEUMOCYTE CULTURES

Thiazinamium chloride (TCl) stimulated phosphatidylcholine secretion in cultures of adult rat type II pneumocytes in a concentration-dependent manner in the range 10-9-10-6 M. At the optimal concentration, secretion was stimulated by 46% which is approximately half the stimulatory effect of the .beta.-agonists terbutaline and isoproterenol. TCl did not increase the rate of choline incorporation into cellular phosphatidylcholine or of lactate dehydrogenase release so its effect on secretion was not secondary to phosphatidylcholine synthesis or cell injury. Since TCl has antihistaminic properties, we examined the effects of other antihistamines. The H-1 antagonists promethazine, which is structurally similar to thiazinamium, and pyrilamine, which has a different structure, also stimulated secretion but the H-2 antagonist, cimetidine, did not. The effects of TCl and pyrilamine were additive to those of terbutaline, suggesting that the mechanisms of action of the antihistamines and the .beta.-agonist were different. Although we were unable to demonstrate an inhibitory effect of histamine itself on either basal or terbutaline-stimulated phosphatidylcholine secretion, it is possible that histamine plays a regulatory role in lung surfactant secretion.