Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Nov;95(3):689–694. doi: 10.1111/j.1476-5381.1988.tb11694.x

Purine receptors and guinea-pig trachea: evidence for a direct action of ATP.

L A Welford 1, W H Anderson 1
PMCID: PMC1854235  PMID: 3207987

Abstract

1. Adenosine (3-300 microM) and ATP (1-300 microM) each induced concentration-dependent relaxation of guinea-pig isolated tracheal preparations that had been precontracted with methacholine. 2. Ectonucleotidase enzymes on the trachea dephosphorylated ATP to form adenosine which was then further metabolised to inosine and hypoxanthine. 3. Dipyridamole (2 microM) inhibited the metabolism of adenosine but did not inhibit the dephosphorylation of ATP. Nevertheless dipyridamole potentiated the effects of both adenosine and ATP in relaxing tracheal smooth muscle. 4. Although adenosine 5'-[beta,gamma-imido] triphosphate (AMP-PNP), an analogue of ATP, was resistant to catabolism by ectonucleotidases, it was more potent at inducing relaxation than either ATP or adenosine, and was also potentiated by dipyridamole (2 microM). 5. Relaxations induced by ATP and by AMP-PNP were more rapid than those induced by adenosine. 6. We therefore conclude that the intact ATP molecule can itself induce relaxation of the guinea-pig trachea, without first having to be metabolised to adenosine, and furthermore that dipyridamole does not act simply by inhibiting the degradation (or uptake) of adenosine.

Full text

PDF
689

Selected References

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

  1. BUNAG R. D., DOUGLAS C. R., IMAI S., BERNE R. M. INFLUENCE OF A PYRIMIDOPYRIMIDINE DERIVATIVE ON DEAMINATION OF ADENOSINE BY BLOOD. Circ Res. 1964 Jul;15:83–88. doi: 10.1161/01.res.15.1.83. [DOI] [PubMed] [Google Scholar]
  2. Blass K. E., Block H. U., Förster W., Pönicke K. Dipyridamole: a potent stimulator of prostacyclin (PGI2) biosynthesis. Br J Pharmacol. 1980 Jan;68(1):71–73. doi: 10.1111/j.1476-5381.1980.tb10700.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown C. M., Collis M. G. Evidence for an A2/Ra adenosine receptor in the guinea-pig trachea. Br J Pharmacol. 1982 Jul;76(3):381–387. doi: 10.1111/j.1476-5381.1982.tb09231.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Christie J., Satchell D. G. Purine receptors in the trachea: is there a receptor for ATP? Br J Pharmacol. 1980 Dec;70(4):512–514. doi: 10.1111/j.1476-5381.1980.tb09768.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coleman R. A. Effects of some purine derivatives on the guinea-pig trachea and their interaction with drugs that block adenosine uptake. Br J Pharmacol. 1976 May;57(1):51–57. doi: 10.1111/j.1476-5381.1976.tb07655.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Farmer J. B., Farrar D. G. Pharmacological studies with adenine, adenosine and some phosphorylated derivatives on guinea-pig tracheal muscle. J Pharm Pharmacol. 1976 Oct;28(10):748–752. doi: 10.1111/j.2042-7158.1976.tb04040.x. [DOI] [PubMed] [Google Scholar]
  7. Fredholm B. B., Hedqvist P., Vernet L. Effect of theophylline and other drugs on rabbit renal cyclic nucleotide phosphodiesterase, 5'-nucleotidase and adenosine deaminase. Biochem Pharmacol. 1978;27(24):2845–2850. doi: 10.1016/0006-2952(78)90199-5. [DOI] [PubMed] [Google Scholar]
  8. Hooker C. S., Calkins P. J., Fleisch J. H. On the measurement of vascular and respiratory smooth muscle responses in vitro. Blood Vessels. 1977;14(1):1–11. doi: 10.1159/000158110. [DOI] [PubMed] [Google Scholar]
  9. Jager L. P. Effects of dipyridamole on the smooth muscle cells of the guinea-pig's taenia coli. Arch Int Pharmacodyn Ther. 1976 May;221(1):40–53. [PubMed] [Google Scholar]
  10. Jones T. R., Lefcoe N. M., Hamilton J. T. Pharmacological study of adenosine and related compounds on isolated guinea pig trachea: evidence for more than one type of purine receptor. Can J Physiol Pharmacol. 1980 Nov;58(11):1356–1365. doi: 10.1139/y80-205. [DOI] [PubMed] [Google Scholar]
  11. Kolassa N., Pfleger K., Rummel W. Specificity of adenosine uptake into the heart and inhibition by dipyridamole. Eur J Pharmacol. 1970 Mar;9(3):265–268. doi: 10.1016/0014-2999(70)90221-9. [DOI] [PubMed] [Google Scholar]
  12. Satchell D. Non-adrenergic, non-cholinergic nerves in mammalian airways: their function and the role of purines. Comp Biochem Physiol C. 1982;72(2):189–196. doi: 10.1016/0306-4492(82)90083-1. [DOI] [PubMed] [Google Scholar]
  13. Uotila P., Männistö J. The inactivation of prostaglandin E2 is decreased by dipyridamole and sulfinpyrazone in isolated rat lungs. Prostaglandins. 1981 Mar;21(3):413–416. doi: 10.1016/0090-6980(81)90086-1. [DOI] [PubMed] [Google Scholar]
  14. Venugopalan C. S., Deason R. D., O'Malley N. A., Flory W. Inhibitory effects of selected purine derivatives on guinea pig pulmonary tissues. Res Commun Chem Pathol Pharmacol. 1986 Mar;51(3):297–309. [PubMed] [Google Scholar]
  15. Welford L. A., Cusack N. J., Hourani S. M. ATP analogues and the guinea-pig taenia coli: a comparison of the structure-activity relationships of ectonucleotidases with those of the P2-purinoceptor. Eur J Pharmacol. 1986 Oct 7;129(3):217–224. doi: 10.1016/0014-2999(86)90431-0. [DOI] [PubMed] [Google Scholar]
  16. Welford L. A., Cusack N. J., Hourani S. M. The structure-activity relationships of ectonucleotidases and of excitatory P2-purinoceptors: evidence that dephosphorylation of ATP analogues reduces pharmacological potency. Eur J Pharmacol. 1987 Sep 2;141(1):123–130. doi: 10.1016/0014-2999(87)90418-3. [DOI] [PubMed] [Google Scholar]

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

RESOURCES