Purinoceptor agonists stimulate phosphatidylcholine secretion in primary cultures of adult rat type II pneumocytes.
We examined the effect of purinoceptor agonists on phosphatidylcholine secretion in primary cultures of type II pneumocytes from adult rats. Surfactant is a major product of the type II cell and phosphatidylcholine is its principal component. Adenosine, AMP, ADP and ATP stimulated phosphatidylcholine secretion in a concentration-dependent manner. At the optimum concentration (1 mM), adenosine and AMP stimulated phosphatidylcholine secretion more than 2-fold, while ATP stimulated 5-fold and ADP almost 7-fold. Because of the magnitude of the response it is tempting to speculate that secretion of surfactant may be under purinoceptor regulation. None of these agents influenced cellular phosphatidylcholine synthesis or lactate dehydrogenase release into the medium, so the effects were primarily on secretion and were not secondary to effects on synthesis or cell damage. Non-metabolizable analogs of adenosine, 5'-N-ethyl-carboxyamidoadensoine (NECA) and L-N6-phenylisopropyladenosine (L-PIA), stimulated secretion to the same extent as adenosine and the effect of NECA was antagonized by 8-phenyltheophylline, suggesting a P1 purinoceptor-mediated mechanism. The stimulatory effect of ATP was diminished by alpha, beta-methylene ATP but only slightly by 8-phenyltheophylline, suggesting that, although part of the ATP effect could be explained by catabolism to adenosine, the P2 purinoceptor may also be involved in regulation of surfactant secretion.
D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000096:biosynthesis / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013726:Terbutaline / Q000494:pharmacology
D000227:Adenine Nucleotides; D010713:Phosphatidylcholines; D011687:Purines; D011743:Pyrimidines; D000241:Adenosine; D013726:Terbutaline; D002794:Choline