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. 1984 Oct;83(2):457–462. doi: 10.1111/j.1476-5381.1984.tb16507.x

Purinoceptor mediated stimulation of prostacyclin release in the porcine pulmonary vasculature.

P G Hellewell, J D Pearson
PMCID: PMC1987114  PMID: 6091831

Abstract

Prostacyclin (PGI2) release from the piglet isolated perfused lung was measured by radioimmunoassay of 6-keto-PGF1 alpha in the venous effluent. Basal release of PGI2 was transiently stimulated up to 30 fold, in a dose-dependent manner, by bolus injections of ATP (0.03-3 mumol). A continuous infusion of ATP also produced a transient response. Dose-response curves for purinergic stimulation of PGI2 release showed that ADP was equipotent with ATP, while AMP and adenosine were virtually inactive. The non-hydrolyzable ATP analogue, ATP-gamma-S, elicited PGI2 release of similar magnitude and duration to that of ATP, suggesting that pulmonary catabolism of ATP is not required to induce PGI2 release. The results suggest that the porcine pulmonary vasculature possesses P2-purinoceptors through which the synthesis and release of PGI2 can be mediated.

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Selected References

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  1. Ager A., Gordon J. L., Moncada S., Pearson J. D., Salmon J. A., Trevethick M. A. Effects of isolation and culture on prostaglandin synthesis by porcine aortic endothelial and smooth muscle cells. J Cell Physiol. 1982 Jan;110(1):9–16. doi: 10.1002/jcp.1041100103. [DOI] [PubMed] [Google Scholar]
  2. Al-Ubaidi F., Bakhle Y. S. Differences in biological activation of arachidonic acid in perfused lungs from guinea pig, rat and man. Eur J Pharmacol. 1980 Mar 7;62(1):89–96. doi: 10.1016/0014-2999(80)90484-7. [DOI] [PubMed] [Google Scholar]
  3. Blair I. A., Barrow S. E., Waddell K. A., Lewis P. J., Dollery C. T. Prostacyclin is not a circulating hormone in man. Prostaglandins. 1982 Apr;23(4):579–589. doi: 10.1016/0090-6980(82)90118-6. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Burnstock G., Cocks T., Paddle B., Staszewska-Barczak J. Evidence that prostaglandin is responsible for the 'rebound contraction' following stimulation of non-adrenergic, non-cholinergic ('purinergic') inhibitory nerves. Eur J Pharmacol. 1975 Apr;31(2):360–362. doi: 10.1016/0014-2999(75)90060-6. [DOI] [PubMed] [Google Scholar]
  6. Collier H. O., James G. W., Schneider C. Antagonism by aspirin and fenamates of bronchoconstriction and nociception induced by adenosine-5'-triphosphate. Nature. 1966 Oct 22;212(5060):411–412. doi: 10.1038/212411a0. [DOI] [PubMed] [Google Scholar]
  7. Cusack N. J., Pearson J. D., Gordon J. L. Stereoselectivity of ectonucleotidases on vascular endothelial cells. Biochem J. 1983 Sep 15;214(3):975–981. doi: 10.1042/bj2140975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dawson W., Boot J. R., Cockerill A. F., Mallen D. N., Osborne D. J. Release of novel prostaglandins and thromboxanes after immunological challenge of guinea pig lung. Nature. 1976 Aug 19;262(5570):699–702. doi: 10.1038/262699a0. [DOI] [PubMed] [Google Scholar]
  10. Fedan J. S., Hogaboom G. K., Westfall D. P., O'Donnell J. P. Comparison of contractions of the smooth muscle of the guinea-pig vas deferens induced by ATP and related nucleotides. Eur J Pharmacol. 1982 Jul 9;81(2):193–204. doi: 10.1016/0014-2999(82)90437-x. [DOI] [PubMed] [Google Scholar]
  11. Gordon J. L., Martin W. Endothelium-dependent relaxation of the pig aorta: relationship to stimulation of 86Rb efflux from isolated endothelial cells. Br J Pharmacol. 1983 Jun;79(2):531–541. doi: 10.1111/j.1476-5381.1983.tb11028.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gordon J. L., Martin W. Stimulation of endothelial prostacyclin production plays no role in endothelium-dependent relaxation of the pig aorta. Br J Pharmacol. 1983 Sep;80(1):179–186. doi: 10.1111/j.1476-5381.1983.tb11064.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hellewell P. G., Pearson J. D. Effect of sulphasalazine on pulmonary inactivation of prostaglandin F2 alpha in the pig. Br J Pharmacol. 1982 Jun;76(2):319–326. doi: 10.1111/j.1476-5381.1982.tb09223.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hellewell P. G., Pearson J. D. Metabolism of circulating adenosine by the porcine isolated perfused lung. Circ Res. 1983 Jul;53(1):1–7. doi: 10.1161/01.res.53.1.1. [DOI] [PubMed] [Google Scholar]
  15. Hemker D. P., Shebuski R. J., Aiken J. W. Release of a prostacyclin-like substance into the circulation of dogs by intravenous adenosine 5'-diphosphate. J Pharmacol Exp Ther. 1980 Feb;212(2):246–252. [PubMed] [Google Scholar]
  16. Isakson P. C., Raz A., Denny S. E., Wyche A., Needleman P. Hormonal stimulation of arachidonate release from isolated perfused organs. Relationship to prostaglandin biosynthesis. Prostaglandins. 1977 Nov;14(5):853–871. doi: 10.1016/0090-6980(77)90302-1. [DOI] [PubMed] [Google Scholar]
  17. Korbut R., Boyd J., Eling T. Respiratory movements alter the generation of prostacyclin and thromboxane A2 in isolated rat lungs: the influence of arachidonic acid-pathway inhibitors on the ratio between pulmonary prostacyclin and thromboxane A2. Prostaglandins. 1981 Mar;21(3):491–503. doi: 10.1016/0090-6980(81)90094-0. [DOI] [PubMed] [Google Scholar]
  18. Lollar P., Owen W. G. Active-site-dependent, thrombin-induced release of adenine nucleotides from cultured human endothelial cells. Ann N Y Acad Sci. 1981;370:51–56. doi: 10.1111/j.1749-6632.1981.tb29720.x. [DOI] [PubMed] [Google Scholar]
  19. Moncada S. Eighth Gaddum Memorial Lecture. University of London Institute of Education, December 1980. Biological importance of prostacyclin. Br J Pharmacol. 1982 May;76(1):3–31. doi: 10.1111/j.1476-5381.1982.tb09186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
  21. Mullane K. M., Moncada S. Prostacyclin release and the modulation of some vasoactive hormones. Prostaglandins. 1980 Jul;20(1):25–49. doi: 10.1016/0090-6980(80)90004-0. [DOI] [PubMed] [Google Scholar]
  22. Needleman P., Marshall G. R., Sobel B. E. Hormone interactions in the isolated rabbit heart. Synthesis and coronary vasomotor effects of prostaglandins, angiotensin, and bradykinin. Circ Res. 1975 Dec;37(6):802–808. doi: 10.1161/01.res.37.6.802. [DOI] [PubMed] [Google Scholar]
  23. Needleman P., Minkes M. S., Douglas J. R., Jr Stimulation of prostaglandin biosynthesis by adenine nucleotides. Profile of prostaglandin release by perfused organs. Circ Res. 1974 Apr;34(4):455–460. doi: 10.1161/01.res.34.4.455. [DOI] [PubMed] [Google Scholar]
  24. Pearson J. D., Gordon J. L. Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides. Nature. 1979 Oct 4;281(5730):384–386. doi: 10.1038/281384a0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Piper P. J., Tippins J. R., Samhoun M. N., Morris H. R., Taylor G. W., Jones C. M. SRS-A and its formation by the lung. Bull Eur Physiopathol Respir. 1981;17(4):571–583. [PubMed] [Google Scholar]
  27. Schwartzman M., Pinkas R., Raz A. Evidence for different purinergic receptors for ATP and ADP in rabbit kidney and heart. Eur J Pharmacol. 1981 Sep 11;74(2-3):167–173. doi: 10.1016/0014-2999(81)90527-6. [DOI] [PubMed] [Google Scholar]
  28. Weksler B. B., Ley C. W., Jaffe E. A. Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and the ionophore A 23187. J Clin Invest. 1978 Nov;62(5):923–930. doi: 10.1172/JCI109220. [DOI] [PMC free article] [PubMed] [Google Scholar]

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