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. 1985 Mar;84(3):765–771. doi: 10.1111/j.1476-5381.1985.tb16159.x

Adenosine and dipyridamole: actions and interactions on the contractile response of guinea-pig ileum to high frequency electrical field stimulation.

E Hayashi, T Maeda, K Shinozuka
PMCID: PMC1987152  PMID: 3986434

Abstract

The action of adenosine on the myenteric plexus-longitudinal muscle strips from guinea-pig ileum to high frequency electrical field stimulation (10 Hz) was investigated. Electrically induced contractions were reduced markedly by tetrodotoxin (0.2 microM) and atropine (1 microM), and partially by noradrenaline (3 microM) and morphine (3 microM). Adenosine, adenosine 5'-monophosphate (AMP) and adenosine triphosphate (ATP) produced a concentration-dependent inhibition of the high frequency contractions over the range of 0.1-100 microM, the most potent being adenosine. The concentration-response curve for adenosine was significantly shifted to the left by dipyridamole (10 nM), while dipyridamole at higher concentrations (30 nM-10 microM), depressed the contraction markedly by itself. Dipyridamole decreased [3H]-adenosine uptake into strips of ileum in a concentration-dependent manner. There was a significant correlationship between the reduction of adenosine uptake and the inhibition of the contraction induced by dipyridamole (r = 0.970). In strips desensitized to adenosine or treated with adenosine deaminase, the inhibitory effect of dipyridamole was significantly reduced. The present investigation revealed that adenosine depressed responses of guinea-pig ileum to high frequency electrical stimulation and suggested that the inhibitory effect of dipyridamole may be closely associated with the behaviour of endogenous adenosine or related compounds.

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Selected References

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  1. Ambache N., Freeman M. A. Atropine-resistant longitudinal muscle spasms due to excitation of non-cholinergic neurones in Auerbach's plexus. J Physiol. 1968 Dec;199(3):705–727. doi: 10.1113/jphysiol.1968.sp008674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burnstock G. Purinergic nerves. Pharmacol Rev. 1972 Sep;24(3):509–581. [PubMed] [Google Scholar]
  3. 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]
  4. Ginsborg B. L., Hirst G. D. The effect of adenosine on the release of the transmitter from the phrenic nerve of the rat. J Physiol. 1972 Aug;224(3):629–645. doi: 10.1113/jphysiol.1972.sp009916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hayashi E., Kunitomo M., Mori M., Shinozuka K., Yamada S. The development of tachyphylaxis to electrical stimulation in guinea-pig ileal longitudinal muscles and the possible participation of adenosine and adenine nucleotides. Br J Pharmacol. 1978 Jul;63(3):457–464. doi: 10.1111/j.1476-5381.1978.tb07797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hayashi E., Mori M., Yamada S., Kumitomo M. Effects of purine compounds on cholinergic nerves. Specificity of adenosine and related compounds on acetylcholine release in electircally stimulated guinea pig ileum. Eur J Pharmacol. 1978 Apr 1;48(3):297–307. doi: 10.1016/0014-2999(78)90088-2. [DOI] [PubMed] [Google Scholar]
  7. Hayashi E., Yamada S., Mori M. Comparative studies on anti-nicotinic action of hexamethonium, mecamylamine and adenosine in the guinea pig isolated ileum. Jpn J Pharmacol. 1977 Oct;27(5):659–665. doi: 10.1254/jjp.27.659. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Kalsner S. Adenosine and dipyridamole actions and interactions on isolated coronary artery strips of cattle. Br J Pharmacol. 1975 Nov;55(3):439–445. doi: 10.1111/j.1476-5381.1975.tb06949.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Kolassa N., Pfleger K., Träm M. Species differences in action and elimination of adenosine after dipyridamole and hexobendine. Eur J Pharmacol. 1971;13(3):320–325. doi: 10.1016/0014-2999(71)90221-4. [DOI] [PubMed] [Google Scholar]
  12. Kuroda Y. Physiological roles of adenosine derivatives which are released during neurotransmission in mammalian brain. J Physiol (Paris) 1978;74(5):463–470. [PubMed] [Google Scholar]
  13. Maske R., Orlandi B., Dowdle E. B. Conractile responses of guinea-pig ileum to high-frequency electrical field stimulation. Eur J Pharmacol. 1980 Oct 3;67(1):47–52. doi: 10.1016/0014-2999(80)90007-2. [DOI] [PubMed] [Google Scholar]
  14. McInnes L., Parratt J. R. Studies on the mode of action of hexobendine, a prospective anti-anginal drug. Br J Pharmacol. 1969 Sep;37(1):272–282. doi: 10.1111/j.1476-5381.1969.tb09544.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moody C. J., Burnstock G. Evidence for the presence of P1-purinoceptors on cholinergic nerve terminals in the guinea-pig ileum. Eur J Pharmacol. 1982 Jan 8;77(1):1–9. doi: 10.1016/0014-2999(82)90527-1. [DOI] [PubMed] [Google Scholar]
  16. Okwasaba F. K., Hamilton J. T., Cook M. A. Antagonism by methylxanthines of purine nucleotide-and dipyridamole-induced inhibition of peristaltic activity of the guinea pig ileum. Eur J Pharmacol. 1977 May 15;43(2):181–194. doi: 10.1016/0014-2999(77)90130-3. [DOI] [PubMed] [Google Scholar]
  17. PATON W. D. CHOLINERGIC TRANSMISSION AND ACETYLCHOLINE OUTPUT. Can J Biochem Physiol. 1963 Dec;41:2637–2653. [PubMed] [Google Scholar]
  18. Paton W. D., Vizi E. S. The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. Br J Pharmacol. 1969 Jan;35(1):10–28. doi: 10.1111/j.1476-5381.1969.tb07964.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reese J. H., Cooper J. R. Modulation of the release of acetylcholine from ileal synaptosomes by adenosine and adenosine 5'-triphosphate. J Pharmacol Exp Ther. 1982 Dec;223(3):612–616. [PubMed] [Google Scholar]
  20. Satchell D. G., Burnstock G. Comparison of the inhibitory effects on the guinea-pig taenia coli of adenine nucleotides and adenosine in the presence and absence of dipyridamole. Eur J Pharmacol. 1975 Jun-Jul;32(02):324–328. doi: 10.1016/0014-2999(75)90299-x. [DOI] [PubMed] [Google Scholar]
  21. Satchell D. G., Lynch A., Bourke P. M., Burnstock G. Potentiation of the effects of exogenously applied ATP and purinergic nerve stimulation on the guinea-pig taenia coli by dipyridamole and hexobendine. Eur J Pharmacol. 1972 Sep;19(3):343–350. doi: 10.1016/0014-2999(72)90100-8. [DOI] [PubMed] [Google Scholar]
  22. Satchell D. G. Nucleotide pyrophosphatase antagonizes responses to adenosine 5'-triphosphate and non-adrenergic, non-cholinergic inhibitory nerve stimulation in the guinea-pig isolated taenia coli. Br J Pharmacol. 1981 Oct;74(2):319–321. doi: 10.1111/j.1476-5381.1981.tb09973.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sawynok J., Jhamandas K. H. Inhibition of acetylcholine release from cholinergic nerves by adenosine, adenine nucleotides and morphine: antagonism by theophylline. J Pharmacol Exp Ther. 1976 May;197(2):379–390. [PubMed] [Google Scholar]
  24. Stafford A. Potentiation of adenosine and the adenine nucleotides by dipyridamole. Br J Pharmacol Chemother. 1966 Nov;28(2):218–227. doi: 10.1111/j.1476-5381.1966.tb01888.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Su C. Neurogenic release of purine compounds in blood vessels. J Pharmacol Exp Ther. 1975 Oct;195(1):159–166. [PubMed] [Google Scholar]
  26. Takagi K., Takayanagi I. Effects of strychnine, derivatives of phenyl acetate and catecholamines on contraction and acetylcholine output from the cholinergic nerve ending of guinea pig ileum. Jpn J Pharmacol. 1966 Jun;16(2):211–216. doi: 10.1254/jjp.16.211. [DOI] [PubMed] [Google Scholar]
  27. Vizi E. S., Knoll J. The inhibitory effect of adenosine and related nucleotides on the release of acetylcholine. Neuroscience. 1976;1(5):391–398. doi: 10.1016/0306-4522(76)90132-9. [DOI] [PubMed] [Google Scholar]

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