Surfactant secretion: evidence that cholinergic stimulation of secretion is indirect

There is strong evidence that cholinergic agents stimulate the secretion of surfactant in vivo and in the isolated perfused lung and that they do not stimulate surfactant secretion in isolated type 2 alveolar cells. These observations suggest that in multicellular systems the cholinergic effect is indirect. In the present work we have accrued the following support for this hypothesis. 1) Propranolol blocked the in vivo stimulation of disaturated phosphatidylcholine (DSPC) secretion by pilocarpine. 2) Bilateral adrenalectomy decreased by 50% the in vivo stimulation of DSPC secretion by pilocarpine. 3) Bilateral vagotomy did not block the increased secretion of DSPC produced in vivo by periodic deep inflations. 4) Pilocarpine (10(-7) M) stimulated DSPC secretion in the isolated perfused lung, and this effect was blocked by indomethacin as well as by atropine. We conclude that cholinergic stimulation of the secretion of surfactant in rats is indirect, i.e., cholinergic agonists do not stimulate the secretion of surfactant by acting directly on type 2 alveolar cells.