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. 1980 Mar;68(3):551–561. doi: 10.1111/j.1476-5381.1980.tb14571.x

Inhibitory effect of adenosine and adenine nucleotides on potassium-evoked efflux of [3H]-noradrenaline from the rat isolated heart: lack of relationship to prostaglandins.

M T Khan, K U Malik
PMCID: PMC2044218  PMID: 7052345

Abstract

1 In the isolated heart of the rat prelabelled with [3H]-noradrenaline (NA) and perfused with Krebs solution, administration of potassium (K+ 60 mumol) increased the efflux of total radioactivity and of [3H]-NA in the perfusate. 2 Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine, but not inosine, dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP) or db cyclic GMP reduced the K+/-evoked overflow of total radioactivity and of intact [3H]-NA, in concentrations too low to cause release of prostaglandins. ATP, ADP and adenosine did not affect tyramine-evoked overflow of tritium. 3 Blockade of prostaglandin synthesis with indomethacin did not alter the inhibitory effect of either ATP, ADP or adenosine on K+/-induced overflow of tritium, thereby indicating that these nucleotides inhibit adrenergic transmission by a mechanism unrelated to stimulation of prostaglandin synthesis. 4 Theophylline which increases entry of calcium (Ca2+) across the cell membrane and reduces its binding in the cell, enhanced K+/-evoked overflow of tritium and diminished the inhibitory effect of ATP, ADP and adenosine on K+/-evoked overflow of tritium from the heart, presumably by interfering with transneuronal Ca2+ metabolism.

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Selected References

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  1. Anton A. H., Sayre D. F. Distribution of metanephrine and normetanephrine in various animals and their analysis in diverse biologic material. J Pharmacol Exp Ther. 1966 Jul;153(1):15–29. [PubMed] [Google Scholar]
  2. BERNE R. M. Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. Am J Physiol. 1963 Feb;204:317–322. doi: 10.1152/ajplegacy.1963.204.2.317. [DOI] [PubMed] [Google Scholar]
  3. BUTCHER R. W., SUTHERLAND E. W. Adenosine 3',5'-phosphate in biological materials. I. Purification and properties of cyclic 3',5'-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3',5'-phosphate in human urine. J Biol Chem. 1962 Apr;237:1244–1250. [PubMed] [Google Scholar]
  4. Bellemann P., Scholz H. Relationship between theophylline uptake and inotropic effect in the guinea-pig heart. Br J Pharmacol. 1974 Oct;52(2):265–274. doi: 10.1111/j.1476-5381.1974.tb09709.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blinks J. R., Olson C. B., Jewell B. R., Bravený P. Influence of caffeine and other methylxanthines on mechanical properties of isolated mammalian heart muscle. Evidence for a dual mechanism of action. Circ Res. 1972 Apr;30(4):367–392. doi: 10.1161/01.res.30.4.367. [DOI] [PubMed] [Google Scholar]
  6. Douglas W. W. Stimulus-secretion coupling: the concept and clues from chromaffin and other cells. Br J Pharmacol. 1968 Nov;34(3):451–474. doi: 10.1111/j.1476-5381.1968.tb08474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Enero M. A., Saidman B. Q. Possible feed-back inhibition of noradrenaline release by purine compounds. Naunyn Schmiedebergs Arch Pharmacol. 1977 Mar;297(1):39–46. doi: 10.1007/BF00508808. [DOI] [PubMed] [Google Scholar]
  8. Fredholm B. B., Hedqvist P. Release of 3H-purines from [3H]-adenine labelled rabbit kidney following sympathetic nerve stimulation, and its inhibition by alpha-adrenoceptor blockage. Br J Pharmacol. 1978 Oct;64(2):239–245. doi: 10.1111/j.1476-5381.1978.tb17295.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hedqvist P., Fredholm B. B. Effects of adenosine on adrenergic neurotransmission; prejunctional inhibition and postjunctional enhancement. Naunyn Schmiedebergs Arch Pharmacol. 1976 Jun;293(3):217–223. doi: 10.1007/BF00507344. [DOI] [PubMed] [Google Scholar]
  10. Hedqvist P., Fredholm B. B., Olundh S. Antagonistic effects of theophylline and adenosine on adrenergic neuroeffector transmission in the rabbit kidney. Circ Res. 1978 Oct;43(4):592–598. doi: 10.1161/01.res.43.4.592. [DOI] [PubMed] [Google Scholar]
  11. Kirpekar S. M., Wakade A. R. Release of noradrenaline from the cat spleen by potassium. J Physiol. 1968 Feb;194(3):595–608. doi: 10.1113/jphysiol.1968.sp008427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lindmar R., Löffelholz K., Muscholl E. Unterschiede zwischen Tyramin und Dimethylphenylpiperzin in der Ca-Abhangigkeit und im zeitlichen Verlauf der Noradrenalin-Freisetzung am isolierten Kaninchenherzen. Experientia. 1967 Nov 15;23(11):933–934. doi: 10.1007/BF02136230. [DOI] [PubMed] [Google Scholar]
  13. Malik K. U., McGiff J. C. Relationship of glucose metabolism to adrenergic transmission in rat mesenteric arteries. Effects of glucose deprivation, glucose metabolites, and changes in ionic composition on adrenergic mechanisms. Circ Res. 1974 Oct;35(4):553–574. doi: 10.1161/01.res.35.4.553. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Olsson R. A., Davis C. J., Khouri E. M., Patterson R. E. Evidence for an adenosine receptor on the surface of dog coronary myocytes. Circ Res. 1976 Jul;39(1):93–98. doi: 10.1161/01.res.39.1.93. [DOI] [PubMed] [Google Scholar]
  16. Su C. Neurogenic release of purine compounds in blood vessels. J Pharmacol Exp Ther. 1975 Oct;195(1):159–166. [PubMed] [Google Scholar]
  17. Su C. Purinergic inhibition of adrenergic transmission in rabbit blood vessels. J Pharmacol Exp Ther. 1978 Feb;204(2):351–361. [PubMed] [Google Scholar]
  18. VANE J. R. THE USE OF ISOLATED ORGANS FOR DETECTING ACTIVE SUBSTANCES IN THE CIRCULATING BLOOD. Br J Pharmacol Chemother. 1964 Oct;23:360–373. doi: 10.1111/j.1476-5381.1964.tb01592.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  20. Verhaeghe R. H., Shepherd J. T. Effect of nitroprusside on smooth muscle and adrenergic nerve terminals in isolated blood vessels. J Pharmacol Exp Ther. 1976 Oct;199(1):269–277. [PubMed] [Google Scholar]
  21. Verhaeghe R. H., Vanhoutte P. M., Shepherd J. T. Inhibition of sympathetic neurotransmission in canine blood vessels by adenosine and adenine nucleotides. Circ Res. 1977 Feb;40(2):208–215. doi: 10.1161/01.res.40.2.208. [DOI] [PubMed] [Google Scholar]
  22. Wakade A. R., Wakade T. D. Inhibition of noradrenaline release by adenosine. J Physiol. 1978 Sep;282:35–49. doi: 10.1113/jphysiol.1978.sp012446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wennmalm A. Prostaglandin-mediated inhibition of noradrenaline release: III. Separation of prostaglandins released from stimulated hearts and analysis of their neurosecretion inhibitory capacity. Prostaglandins. 1978 Jan;15(1):113–121. doi: 10.1016/s0090-6980(78)80009-4. [DOI] [PubMed] [Google Scholar]
  24. Wooten G. F., Thoa N. B., Kopin I. J., Axelrod J. Enhanced release of dopamine -hydroxylase and norepinephrine from sympathetic nerves by dibutyryl cyclic adenosine 3', 5'-monophosphate and theophylline. Mol Pharmacol. 1973 Mar;9(2):178–183. [PubMed] [Google Scholar]

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