Pyridine derivatives stimulate phosphatidylcholine secretion in primary cultures of rat type II pneumocytes.
We have examined the effects of pyridine derivatives on phosphatidylcholine secretion in primary cultures of rat type II pneumocytes. Of 12 pyridine derivatives, 4-aminopyridine, 4-dimethylaminopyridine and 4-pyrolidinopyridine had a stimulatory effect on phosphatidylcholine secretion, whereas other derivatives had little effect. The stimulatory effect 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 microM), an intracellular Ca2+ chelator. In addition, the stimulatory effect of 4-aminopyridine was suppressed by W-7(N-(6-aminohexyl)-5-chloro-1-napthalene-sulphonamide)(10 microM), a calmodulin inhibitor, and sphingosine (10 microM) and staurosporine (0-1 microM), protein kinase C inhibitors. These results indicate that several pyridine derivatives stimulate phosphatidylcholine secretion in type II pneumocytes.
Kai
H
H
Department of Pharmacological Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Murahara
K
K
Isohama
Y
Y
Takahama
K
K
Oda
Y
Y
Hamamura
I
I
Yoshitake
K
K
Miyata
T
T
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D002614:Chelating Agents; D010713:Phosphatidylcholines; D011725:Pyridines; D013449:Sulfonamides; D014665:Vasodilator Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C021249:4-pyrrolidinopyridine; D004533:Egtazic Acid; C017967:W 7; D015761:4-Aminopyridine; D007770:L-Lactate Dehydrogenase; C003885:4-dimethylaminopyridine; D002118:Calcium