Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1983 Dec;80(4):727–734. doi: 10.1111/j.1476-5381.1983.tb10064.x

Antagonism of enkephalin action on acetylcholine release by methylxanthines: lack of a purine link.

J Elliott, K Jhamandas, H Notman, M Sutak
PMCID: PMC2045056  PMID: 6571228

Abstract

Theophylline (Theo) and caffeine antagonized the inhibitory effect of methionine (Met)-enkephalin, leucine (Leu)-enkephalin and morphine on the twitch height of the field stimulated myenteric plexus longitudinal muscle (MPLM) preparation of the guinea-pig ileum. Antagonism by Theo was observed only in tissues stimulated submaximally, but that by caffeine was observed in tissues stimulated submaximally and supramaximally. Injection of Theo (20, 40 mg kg-1) or caffeine (40 mg kg-1) reversed or blocked the inhibitory effects of Leu-enkephalin (50 micrograms i.c.v.) and a systemically active enkephalin FK 33,824 (0.5 mg kg-1) on the release of acetylcholine (ACh) from the rat cortex in vivo. Injections of morphine (2.5, 5.0 mg kg-1 i.v.) did not modify the in vivo release of radiolabelled purines from the cerebral cortex prelabelled with [3H]-adenosine (2.8 X 10(-7) M). Application of K+ (60 mM) to the cortex readily stimulated this release. Injection of morphine (5.0 mg kg-1 i.v.) increased the spontaneous release of radiolabelled purines from the cortex prelabelled with a higher concentration of [3H]-adenosine (10(-4) M) in six out of eleven experiments. Under similar conditions neither Leu-enkephalin (50 micrograms i.c.v.) nor FK 33,824 (0.5 mg kg-1 i.v.) stimulated purine release. It is concluded that methylxanthines can antagonize the inhibitory action of opioids on the peripheral and central release of ACh. However, this antagonism does not reflect an intermediary purine step in the action of opioids on the release of ACh.

Full text

PDF
727

Selected References

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

  1. Aranda J. V., Turmen T. Methylxanthines in apnea of prematurity. Clin Perinatol. 1979 Mar;6(1):87–108. [PubMed] [Google Scholar]
  2. Brailowsky S., Guerrero-Muñoz F., Luján M., Shkurovich M. Morphine-theophylline interaction: antagonism or facilitation? Br J Pharmacol. 1981 Aug;73(4):887–892. doi: 10.1111/j.1476-5381.1981.tb08742.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chapman R. A., Miller D. J. The effects of caffeine on the contraction of the frog heart. J Physiol. 1974 Nov;242(3):589–613. doi: 10.1113/jphysiol.1974.sp010725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Daly J. W., Bruns R. F., Snyder S. H. Adenosine receptors in the central nervous system: relationship to the central actions of methylxanthines. Life Sci. 1981 May 11;28(19):2083–2097. doi: 10.1016/0024-3205(81)90614-7. [DOI] [PubMed] [Google Scholar]
  5. Fredholm B. B., Vernet L. Morphine increases depolarization induced purine release from rat cortical slices. Acta Physiol Scand. 1978 Dec;104(4):502–504. doi: 10.1111/j.1748-1716.1978.tb06308.x. [DOI] [PubMed] [Google Scholar]
  6. Gallant C. A., Clement J. G. Methylxanthines antagonize adenosine but not morphine inhibition in guinea pig ileum. Can J Physiol Pharmacol. 1981 Aug;59(8):886–889. doi: 10.1139/y81-133. [DOI] [PubMed] [Google Scholar]
  7. Guerrero-Munoz F., Cerreta K. V., Guerrero M. L., Way E. L. Effect of morphine on synaptosomal Ca++ uptake. J Pharmacol Exp Ther. 1979 Apr;209(1):132–136. [PubMed] [Google Scholar]
  8. Jhamandas K., Dumbrille A. Regional release of [3H]adenosine derivatives from rat brain in vivo: effect of excitatory amino acids, opiate agonists, and benzodiazepines. Can J Physiol Pharmacol. 1980 Nov;58(11):1262–1278. doi: 10.1139/y80-193. [DOI] [PubMed] [Google Scholar]
  9. Jhamandas K., Elliott J. Investigation of action of enkephalin on the spontaneous and evoked release of acetylcholine from rat cortical and striatal slices. Br J Pharmacol. 1980;71(1):211–217. doi: 10.1111/j.1476-5381.1980.tb10928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jhamandas K., Hron V., Sutak M. Comparative effects of opiate agonists methadone, levorphanol, and their isomers on the release of cortical ACh in vivo and in vitro. Can J Physiol Pharmacol. 1975 Aug;53(4):540–548. doi: 10.1139/y75-076. [DOI] [PubMed] [Google Scholar]
  11. Jhamandas K., Sawynok J., Sutak M. Antagonism of morphine action on brain acetylcholine release by methylxanthines and calcium. Eur J Pharmacol. 1978 Jun 1;49(3):309–312. doi: 10.1016/0014-2999(78)90108-5. [DOI] [PubMed] [Google Scholar]
  12. Jhamandas K., Sutak M. Action of enkephalin analogues and morphine on brain acetylcholine release: differential reversal by naloxone and an opiate pentapeptide. Br J Pharmacol. 1980;71(1):201–210. doi: 10.1111/j.1476-5381.1980.tb10927.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jhamandas K., Sutak M. Modification of brain acetylcholine release by morphine and its antagonists in normal and morphine-dependent rats. Br J Pharmacol. 1974 Jan;50(1):57–62. doi: 10.1111/j.1476-5381.1974.tb09592.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jhamandas K., Sutak M. Morphine-naloxone interaction in the central cholinergic system: the influence of subcortical lesioning and electrical stimulation. Br J Pharmacol. 1976 Sep;58(1):101–107. doi: 10.1111/j.1476-5381.1976.tb07697.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Opmeer F. A., Van Ree J. M. Competitive antagonism of morphine action in vitro by calcium. Eur J Pharmacol. 1979 Feb 1;53(4):395–397. doi: 10.1016/0014-2999(79)90467-9. [DOI] [PubMed] [Google Scholar]
  16. Perkins M. N., Stone T. W. Blockade of striatal neurone responses to morphine by aminophylline: evidence for adenosine mediation of opiate action. Br J Pharmacol. 1980 May;69(1):131–137. doi: 10.1111/j.1476-5381.1980.tb10892.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Phillis J. W., Jiang Z. G., Chelack B. J., Wu P. H. The effect of morphine on purine and acetylcholine release from rat cerebral cortex: evidence for a purinergic component in morphine's action. Pharmacol Biochem Behav. 1980 Sep;13(3):421–427. doi: 10.1016/0091-3057(80)90249-x. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Sawynok J., Jhamandas K. Interactions of methylxanthines, nonxanthine phosphodiesterase inhibitors, and calcium with morphine in the guinea pig myenteric plexus. Can J Physiol Pharmacol. 1979 Aug;57(8):853–859. doi: 10.1139/y79-130. [DOI] [PubMed] [Google Scholar]
  20. Stone T. W. The effects of morphine and methionine-enkephalin on the release of purines from cerebral cortex slices of rats and mice. Br J Pharmacol. 1981 Sep;74(1):171–176. doi: 10.1111/j.1476-5381.1981.tb09970.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Szerb J. C. Lack of effect of morphine in reducing the release of labelled acetylcholine from brain slices stimulated electrically. Eur J Pharmacol. 1974 Nov;29(1):192–194. doi: 10.1016/0014-2999(74)90191-5. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Vizi E. S., Somogyi G. T., Magyar K. Evidence that morphine and opioid peptides do not share a common pathway with adenosine in inhibiting acetylcholine release from isolated intestine. J Auton Pharmacol. 1981 Dec;1(5):413–419. doi: 10.1111/j.1474-8673.1981.tb00081.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES