Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 Nov;89(3):485–491. doi: 10.1111/j.1476-5381.1986.tb11148.x

P2-purinoceptors regulate surfactant secretion from rat isolated alveolar type II cells.

W R Rice, F M Singleton
PMCID: PMC1917166  PMID: 3801783

Abstract

Rat isolated alveolar Type II cells were utilized to examine the effect of purine and pyrimidine analogues on secretion of pulmonary surfactant. ATP potently stimulated [3H]-phosphatidylcholine ([3H]-PC) secretion in a time- and dose-dependent manner. The effect of ATP was noted by one hour of exposure and persisted for three hours. The EC50 (concentration producing 1/2 the maximal response) for ATP-induced [3H]-PC secretion was 100 nM. ADP was also a potent secretagogue for surfactant secretion, but AMP and adenosine had no significant effect on surfactant secretion at concentrations less than or equal to 250 microM. The EC50 for ADP-induced [3H]-PC secretion was 250 nM. Other purine and pyrimidine nucleotides (ITP, GTP, CTP, TTP) were examined for their effect on [3H]-PC secretion. All purine and pyrimidine triphosphates examined significantly augmented [3H]-PC secretion, but were much less potent than ATP. The EC50s were ITP = 10 microM; GTP = 100 microM; CTP = 250 microM; TTP = 100 microM. Neither 8-phenyltheophylline (10 microM, a P1-purinoceptor antagonist), propranolol (100 microM, a beta-adrenoceptor antagonist), nor indomethacin (10 microM, a prostaglandin synthetase inhibitor) inhibited ATP-induced [3H]-PC secretion from isolated Type II cells. These data provide evidence for regulation of surfactant secretion from alveolar Type II cells by a P2-purinoceptor.

Full text

PDF
486

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banks B. E., Brown C., Burgess G. M., Burnstock G., Claret M., Cocks T. M., Jenkinson D. H. Apamin blocks certain neurotransmitter-induced increases in potassium permeability. Nature. 1979 Nov 22;282(5737):415–417. doi: 10.1038/282415a0. [DOI] [PubMed] [Google Scholar]
  2. Boeynaems J. M., Galand N. Stimulation of vascular prostacyclin synthesis by extracellular ADP and ATP. Biochem Biophys Res Commun. 1983 Apr 15;112(1):290–296. doi: 10.1016/0006-291x(83)91829-6. [DOI] [PubMed] [Google Scholar]
  3. Brown L. A., Longmore W. J. Adrenergic and cholinergic regulation of lung surfactant secretion in the isolated perfused rat lung and in the alveolar type II cell in culture. J Biol Chem. 1981 Jan 10;256(1):66–72. [PubMed] [Google Scholar]
  4. Burnstock G., Cusack N. J., Hills J. M., MacKenzie I., Meghji P. Studies on the stereoselectivity of the P2-purinoceptor. Br J Pharmacol. 1983 Aug;79(4):907–913. doi: 10.1111/j.1476-5381.1983.tb10535.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burnstock G. Purinergic nerves and receptors. Prog Biochem Pharmacol. 1980;16:141–154. [PubMed] [Google Scholar]
  6. Burnstock G. Purinergic nerves. Pharmacol Rev. 1972 Sep;24(3):509–581. [PubMed] [Google Scholar]
  7. Burnstock G. Review lecture. Neurotransmitters and trophic factors in the autonomic nervous system. J Physiol. 1981;313:1–35. doi: 10.1113/jphysiol.1981.sp013648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chapal J., Loubatieres-Mariani M. M. Effects of phosphate-modified adenine nucleotide analogues on insulin secretion from perfused rat pancreas. Br J Pharmacol. 1981 May;73(1):105–110. doi: 10.1111/j.1476-5381.1981.tb16778.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Charest R., Blackmore P. F., Exton J. H. Characterization of responses of isolated rat hepatocytes to ATP and ADP. J Biol Chem. 1985 Dec 15;260(29):15789–15794. [PubMed] [Google Scholar]
  10. Dobbs L. G., Mason R. J. Pulmonary alveolar type II cells isolated from rats. Release of phosphatidylcholine in response to beta-adrenergic stimulation. J Clin Invest. 1979 Mar;63(3):378–387. doi: 10.1172/JCI109313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dobbs L. G., Mason R. J. Stimulation of secretion of disaturated phosphatidylcholine from isolated alveolar type II cells by 12-O-tetradecanoyl-13-phorbol acetate. Am Rev Respir Dis. 1978 Oct;118(4):705–733. doi: 10.1164/arrd.1978.118.4.705. [DOI] [PubMed] [Google Scholar]
  12. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  13. Fedan J. S., Hogaboom G. K., O'Donnell J. P. Comparison of the effects of apamin, a Ca2+-dependent K+ channel blocker, and arylazido aminopropionyl ATP (ANAPP3), a P2-purinergic receptor antagonist, in the guinea-pig vas deferens. Eur J Pharmacol. 1984 Sep 17;104(3-4):327–334. doi: 10.1016/0014-2999(84)90409-6. [DOI] [PubMed] [Google Scholar]
  14. Gallacher D. V. Are there purinergic receptors on parotid acinar cells? Nature. 1982 Mar 4;296(5852):83–86. doi: 10.1038/296083a0. [DOI] [PubMed] [Google Scholar]
  15. Gilfillan A. M., Hollingsworth M., Jones A. W. The pharmacological modulation of [3H]-disaturated phosphatidylcholine overflow from perifused lung slices of adult rats: a new method for the study of lung surfactant secretion. Br J Pharmacol. 1983 Jun;79(2):363–371. doi: 10.1111/j.1476-5381.1983.tb11008.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gilfillan A. M., Rooney S. A. Arachidonic acid metabolites stimulate phosphatidylcholine secretion in primary cultures of type II pneumocytes. Biochim Biophys Acta. 1985 Feb 8;833(2):336–341. doi: 10.1016/0005-2760(85)90207-3. [DOI] [PubMed] [Google Scholar]
  17. Griffith S. G., Meghji P., Moody C. J., Burnstock G. 8-phenyltheophylline: a potent P1-purinoceptor antagonist. Eur J Pharmacol. 1981 Oct 15;75(1):61–64. doi: 10.1016/0014-2999(81)90346-0. [DOI] [PubMed] [Google Scholar]
  18. Hellewell P. G., Pearson J. D. Purinoceptor mediated stimulation of prostacyclin release in the porcine pulmonary vasculature. Br J Pharmacol. 1984 Oct;83(2):457–462. doi: 10.1111/j.1476-5381.1984.tb16507.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Loubatieres-Mariani M. M., Chapal J., Lignon F., Valette G. Structural specificity of nucleotides for insulin secretory action from the isolated perfused rat pancreas. Eur J Pharmacol. 1979 Nov 16;59(3-4):277–286. doi: 10.1016/0014-2999(79)90291-7. [DOI] [PubMed] [Google Scholar]
  20. Marino P. A., Rooney S. A. Surfactant secretion in a newborn rabbit lung slice model. Biochim Biophys Acta. 1980 Dec 5;620(3):509–519. doi: 10.1016/0005-2760(80)90143-5. [DOI] [PubMed] [Google Scholar]
  21. Martin W., Cusack N. J., Carleton J. S., Gordon J. L. Specificity of P2-purinoceptor that mediates endothelium-dependent relaxation of the pig aorta. Eur J Pharmacol. 1985 Feb 5;108(3):295–299. doi: 10.1016/0014-2999(85)90452-2. [DOI] [PubMed] [Google Scholar]
  22. Mason R. J., Dobbs L. G., Greenleaf R. D., Williams M. C. Alveolar type II cells. Fed Proc. 1977 Dec;36(13):2697–2702. [PubMed] [Google Scholar]
  23. Mehta A. K., Kulkarni S. K. Evidence for the presence of P1- and P2-purinoceptors in rat caecum. Arch Int Pharmacodyn Ther. 1983 Aug;264(2):187–194. [PubMed] [Google Scholar]
  24. Mescher E. J., Dobbs L. G., Mason R. J. Cholera toxin stimulates secretion of saturated phosphatidylcholine and increases cellular cyclic AMP in isolated rat alveolar type II cells. Exp Lung Res. 1983 Nov;5(3):173–182. doi: 10.3109/01902148309061512. [DOI] [PubMed] [Google Scholar]
  25. Mettler N. R., Gray M. E., Schuffman S., LeQuire V. S. beta-Adrenergic induced synthesis and secretion of phosphatidylcholine by isolated pulmonary alveolar type II cells. Lab Invest. 1981 Dec;45(6):575–586. [PubMed] [Google Scholar]
  26. Pearson J. D., Slakey L. L., Gordon J. L. Stimulation of prostaglandin production through purinoceptors on cultured porcine endothelial cells. Biochem J. 1983 Jul 15;214(1):273–276. doi: 10.1042/bj2140273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rice W. R., Osterhoudt K. C., Whitsett J. A. Effect of cytochalasins on surfactant release from alveolar type II cells. Biochim Biophys Acta. 1984 Sep 14;805(1):12–18. doi: 10.1016/0167-4889(84)90030-2. [DOI] [PubMed] [Google Scholar]
  28. Sano K., Voelker D. R., Mason R. J. Involvement of protein kinase C in pulmonary surfactant secretion from alveolar type II cells. J Biol Chem. 1985 Oct 15;260(23):12725–12729. [PubMed] [Google Scholar]
  29. Smellie F. W., Davis C. W., Daly J. W., Wells J. N. Alkylxanthines: inhibition of adenosine-elicited accumulation of cyclic AMP in brain slices and of brain phosphodiesterase activity. Life Sci. 1979 Jun 25;24(26):2475–2482. doi: 10.1016/0024-3205(79)90458-2. [DOI] [PubMed] [Google Scholar]
  30. Sussman I., Prettyman R., O'Brien T. G. Phorbol esters and gene expression: the role of rapid changes in K+ transport in the induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate in BALB/c 3T3 cells and a mutant cell line defective in Na+K+Cl- cotransport. J Cell Biol. 1985 Dec;101(6):2316–2323. doi: 10.1083/jcb.101.6.2316. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES