PYRIDINE-DERIVATIVES STIMULATE PHOSPHATIDYLCHOLINE SECRETION IN PRIMARY CULTURES OF RAT TYPE-II PNEUMOCYTES

We have examined the effects of pyridine derivatives on phosphatidylch oline secretion in primary cultures of rat type II pneumocytes. Of 12 pyridine derivatives, 4-aminopyridine, 4-dimethylaminopyridine and 4-p yrolidinopyridine had a stimulatory effect on phosphatidylcholine secr etion, whereas other derivatives had little effect. The stimulatory ef fect of 4-aminopyridine was concentration- and time-dependent, and was inhibited by the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane -N, N, N', N'-tetraacetic acid (3 mu M), an intracellular Ca2+ chelato r. In addition, the stimulatory effect of 4-aminopyridine was suppress ed by W-7 (6-aminohexyl)-5-chloro-1-napthalene-sulphonamide) (10 mu M) , a calmodulin inhibitor, and sphingosine (10 mu M) and staurosporine (0.1 mu M), protein kinase C inhibitors. These results indicate that s everal pyridine derivatives stimulate phosphatidylcholine secretion in type II pneumocytes.