Histamine stimulation of surfactant secretion from rat type II pneumocytes

The present study examined the effect of histamine on the secretion of phosphatidylcholine, the predominant component of pulmonary surfactant from adult rat alveolar type II pneumocytes in primary culture. Histamine stimulated surfactant secretion in a time- and dose-dependent manner. At a concentration of 10 microM, histamine stimulated surfactant release by 5.2-fold over the basal secretory rate. The concentration producing half the maximal response for histamine-induced secretion was 70 nM. Histamine-induced secretion was blocked by both the selective histamine1 receptor antagonist pyrilamine and the selective histamine2 receptor antagonist cimetidine, but not by the beta-adrenergic antagonist alprenolol. Histamine activated adenylate cyclase and intracellular adenosine 3',5'-cyclic monophosphate (cAMP) production. These effects on adenylate cyclase and cAMP induced by histamine were inhibited by the H2 antagonist cimetidine. This would suggest that surfactant secretion was stimulated by histamine through H2 receptors and by cAMP. When histamine and isoproterenol were added concomitantly, the effects on phosphatidylcholine secretion were additive; however, there was no additive effect on adenylate cyclase activation. This coupled with H2 antagonist pyrilamine inhibition of histamine-induced secretion would suggest that histamine stimulated surfactant secretion through another mechanism in addition to a cAMP-dependent mechanism.