Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Feb;90(2):403–412. doi: 10.1111/j.1476-5381.1987.tb08970.x

The adenosine receptor-mediated inhibition of noradrenaline release possibly involves an N-protein and is increased by alpha 2-autoreceptor blockade.

C Allgaier, G Hertting, O V Kügelgen
PMCID: PMC1916948  PMID: 3103806

Abstract

The stimulation-evoked overflow of [3H]-noradrenaline from slices of the rabbit hippocampus is inhibited by alpha 2-autoreceptors as well as by adenosine (A1)-receptors. Slices of rabbit hippocampus were labelled with [3H]-noradrenaline, superfused continuously and stimulated twice electrically (rectangular pulses; 2 ms, 3 Hz, 24 mA, 5 V cm-1). Treatment of hippocampal slices with N-ethylmaleimide (NEM, 30 microM; 30 min), which functionally disturbs certain N-proteins, decreased the inhibitory action of adenosine receptor agonists like (-)-N6-(R-phenylisopropyl)-adenosine ((-)-PIA) and adenosine on noradrenaline release. Release inhibition caused by (-)-PIA (0.03-1 microM) was antagonized by NEM in a non-competitive manner in the absence and in the presence of the alpha 2-adrenoceptor antagonist yohimbine. The adenosine receptor antagonist 8-phenyltheophylline significantly increased the evoked noradrenaline release by about 15% in control slices by diminishing the inhibitory action of endogenous adenosine. In NEM-treated slices this effect of 8-phenyltheophylline was not seen. In the presence of (-)-PIA (0.1 microM), i.e. under conditions of an increased inhibitory tone, release facilitation by 8-phenyltheophylline was decreased by NEM compared to that in the respective controls. Occupation of the A1-receptor with (-)-PIA prior to and during the NEM treatment did not protect the A1-receptor-coupled signal transduction system from being affected by NEM. In the presence of the alpha 2-adrenoceptor antagonist yohimbine, the inhibitory action of (-)-PIA was strongly increased. The above results suggest the involvement of a regulatory N-protein in the A1-receptor-mediated inhibition of noradrenaline release and an interaction between the alpha 2-autoreceptor and the A1-receptor-coupled signal transduction system, possibly at the level of a N-protein.

Full text

PDF
404

Selected References

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

  1. Allgaier C., Feuerstein T. J., Hertting G. N-ethylmaleimide (NEM) diminishes alpha 2-adrenoceptor mediated effects on noradrenaline release. Naunyn Schmiedebergs Arch Pharmacol. 1986 Jun;333(2):104–109. doi: 10.1007/BF00506511. [DOI] [PubMed] [Google Scholar]
  2. Allgaier C., Feuerstein T. J., Jackisch R., Hertting G. Islet-activating protein (pertussis toxin) diminishes alpha 2-adrenoceptor mediated effects on noradrenaline release. Naunyn Schmiedebergs Arch Pharmacol. 1985 Nov;331(2-3):235–239. doi: 10.1007/BF00634243. [DOI] [PubMed] [Google Scholar]
  3. Asano T., Ogasawara N. Uncoupling of gamma-aminobutyric acid B receptors from GTP-binding proteins by N-ethylmaleimide: effect of N-ethylmaleimide on purified GTP-binding proteins. Mol Pharmacol. 1986 Mar;29(3):244–249. [PubMed] [Google Scholar]
  4. Boyer J. L., García A., Posadas C., García-Sáinz J. A. Differential effect of pertussis toxin on the affinity state for agonists of renal alpha 1- and alpha 2- adrenoceptors. J Biol Chem. 1984 Jul 10;259(13):8076–8079. [PubMed] [Google Scholar]
  5. Bruns R. F., Daly J. W., Snyder S. H. Adenosine receptor binding: structure-activity analysis generates extremely potent xanthine antagonists. Proc Natl Acad Sci U S A. 1983 Apr;80(7):2077–2080. doi: 10.1073/pnas.80.7.2077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cockcroft S., Gomperts B. D. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature. 1985 Apr 11;314(6011):534–536. doi: 10.1038/314534a0. [DOI] [PubMed] [Google Scholar]
  7. Cooper D. M. Bimodal regulation of adenylate cyclase. FEBS Lett. 1982 Feb 22;138(2):157–163. doi: 10.1016/0014-5793(82)80431-6. [DOI] [PubMed] [Google Scholar]
  8. Cote T. E., Frey E. A., Sekura R. D. Altered activity of the inhibitory guanyl nucleotide-binding component (Ni) induced by pertussis toxin. Uncoupling of Ni from receptor with continued coupling of Ni to the catalytic unit. J Biol Chem. 1984 Jul 25;259(14):8693–8698. [PubMed] [Google Scholar]
  9. Dolphin A. C., Prestwich S. A. Pertussis toxin reverses adenosine inhibition of neuronal glutamate release. Nature. 1985 Jul 11;316(6024):148–150. doi: 10.1038/316148a0. [DOI] [PubMed] [Google Scholar]
  10. Feuerstein T. J., Hertting G., Jackisch R. Modulation of hippocampal serotonin (5-HT) release by endogenous adenosine. Eur J Pharmacol. 1985 Jan 2;107(2):233–242. doi: 10.1016/0014-2999(85)90063-9. [DOI] [PubMed] [Google Scholar]
  11. Fredholm B. B., Jonzon B., Lindström K. Adenosine receptor mediated increases and decreases in cyclic AMP in hippocampal slices treated with forskolin. Acta Physiol Scand. 1983 Mar;117(3):461–463. doi: 10.1111/j.1748-1716.1983.tb00022.x. [DOI] [PubMed] [Google Scholar]
  12. Fredholm B. B., Lindgren E., Lindström K. Treatment with N-ethylmaleimide selectively reduces adenosine receptor-mediated decreases in cyclic AMP accumulation in rat hippocampal slices. Br J Pharmacol. 1985 Oct;86(2):509–513. doi: 10.1111/j.1476-5381.1985.tb08922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fredholm B. B., Lindgren E. Possible involvement of the Ni-protein in the prejunctional inhibitory effect of a stable adenosine analogue (R-PIA) on noradrenaline release in the rat hippocampus. Acta Physiol Scand. 1986 Feb;126(2):307–309. doi: 10.1111/j.1748-1716.1986.tb07819.x. [DOI] [PubMed] [Google Scholar]
  14. Gilman A. G. G proteins and dual control of adenylate cyclase. Cell. 1984 Mar;36(3):577–579. doi: 10.1016/0092-8674(84)90336-2. [DOI] [PubMed] [Google Scholar]
  15. Harden T. K., Scheer A. G., Smith M. M. Differential modification of the interaction of cardiac muscarinic cholinergic and beta-adrenergic receptors with a guanine nucleotide binding component(s). Mol Pharmacol. 1982 May;21(3):570–580. [PubMed] [Google Scholar]
  16. Harms H. H., Wardeh G., Mulder A. H. Adenosine modulates depolarization-induced release of 3H-noradrenaline from slices of rat brain neocortex. Eur J Pharmacol. 1978 Jun 1;49(3):305–308. doi: 10.1016/0014-2999(78)90107-3. [DOI] [PubMed] [Google Scholar]
  17. Harms H. H., Wardeh G., Mulder A. H. Effect of adenosine on depolarization-induced release of various radiolabelled neurotransmitters from slices of rat corpus striatum. Neuropharmacology. 1979 Jul;18(7):577–580. doi: 10.1016/0028-3908(79)90107-2. [DOI] [PubMed] [Google Scholar]
  18. Hildebrandt J. D., Sekura R. D., Codina J., Iyengar R., Manclark C. R., Birnbaumer L. Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins. Nature. 1983 Apr 21;302(5910):706–709. doi: 10.1038/302706a0. [DOI] [PubMed] [Google Scholar]
  19. Holz G. G., 4th, Rane S. G., Dunlap K. GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels. Nature. 1986 Feb 20;319(6055):670–672. doi: 10.1038/319670a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jackisch R., Fehr R., Hertting G. Adenosine: an endogenous modulator of hippocampal noradrenaline release. Neuropharmacology. 1985 Jun;24(6):499–507. doi: 10.1016/0028-3908(85)90055-3. [DOI] [PubMed] [Google Scholar]
  21. Jackisch R., Geppert M., Illes P. Characterization of opioid receptors modulating noradrenaline release in the hippocampus of the rabbit. J Neurochem. 1986 Jun;46(6):1802–1810. doi: 10.1111/j.1471-4159.1986.tb08499.x. [DOI] [PubMed] [Google Scholar]
  22. Jackisch R., Moll S., Feuerstein T. J., Hertting G. Dopaminergic modulation of hippocampal noradrenaline release. Evidence for alpha 2-antagonistic effects of some dopamine receptor agonists and antagonists. Naunyn Schmiedebergs Arch Pharmacol. 1985 Aug;330(2):105–113. doi: 10.1007/BF00499902. [DOI] [PubMed] [Google Scholar]
  23. Jackisch R., Strittmatter H., Kasakov L., Hertting G. Endogenous adenosine as a modulator of hippocampal acetylcholine release. Naunyn Schmiedebergs Arch Pharmacol. 1984 Oct;327(4):319–325. doi: 10.1007/BF00506243. [DOI] [PubMed] [Google Scholar]
  24. Jackisch R., Werle E., Hertting G. Identification of mechanisms involved in the modulation of release of noradrenaline in the hippocampus of the rabbit in vitro. Neuropharmacology. 1984 Dec;23(12A):1363–1371. doi: 10.1016/0028-3908(84)90074-1. [DOI] [PubMed] [Google Scholar]
  25. Jakobs K. H., Lasch P., Minuth M., Aktories K., Schultz G. Uncoupling of alpha-adrenoceptor-mediated inhibition of human platelet adenylate cyclase by N-ethylmaleimide. J Biol Chem. 1982 Mar 25;257(6):2829–2833. [PubMed] [Google Scholar]
  26. Kurose H., Ui M. Functional uncoupling of muscarinic receptors from adenylate cyclase in rat cardiac membranes by the active component of islet-activating protein, pertussis toxin. J Cyclic Nucleotide Protein Phosphor Res. 1983;9(4-5):305–318. [PubMed] [Google Scholar]
  27. Markstein R., Digges K., Marshall N. R., Starke K. Forskolin and the release of noradrenaline in cerebrocortical slices. Naunyn Schmiedebergs Arch Pharmacol. 1984 Jan;325(1):17–24. doi: 10.1007/BF00507049. [DOI] [PubMed] [Google Scholar]
  28. Murayama T., Ui M. Loss of the inhibitory function of the guanine nucleotide regulatory component of adenylate cyclase due to its ADP ribosylation by islet-activating protein, pertussis toxin, in adipocyte membranes. J Biol Chem. 1983 Mar 10;258(5):3319–3326. [PubMed] [Google Scholar]
  29. Neer E. J., Lok J. M., Wolf L. G. Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase. J Biol Chem. 1984 Nov 25;259(22):14222–14229. [PubMed] [Google Scholar]
  30. Nomura Y., Kitamura Y., Segawa T. Decrease of clonidine binding affinity to alpha 2-adrenoceptor by ADP-ribosylation of 41,000-dalton proteins in rat cerebral cortical membranes by islet-activating protein. J Neurochem. 1985 Feb;44(2):364–369. doi: 10.1111/j.1471-4159.1985.tb05425.x. [DOI] [PubMed] [Google Scholar]
  31. Pedata F., Antonelli T., Lambertini L., Beani L., Pepeu G. Effect of adenosine, adenosine triphosphate, adenosine deaminase, dipyridamole and aminophylline on acetylcholine release from electrically-stimulated brain slices. Neuropharmacology. 1983 May;22(5):609–614. doi: 10.1016/0028-3908(83)90152-1. [DOI] [PubMed] [Google Scholar]
  32. Quennedey M. C., Bockaert J., Rouot B. Direct and indirect effects of sulfhydryl blocking agents on agonist and antagonist binding to central alpha 1- and alpha 2-adrenoceptors. Biochem Pharmacol. 1984 Dec 15;33(24):3923–3928. doi: 10.1016/0006-2952(84)90002-9. [DOI] [PubMed] [Google Scholar]
  33. Rodbell M. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature. 1980 Mar 6;284(5751):17–22. doi: 10.1038/284017a0. [DOI] [PubMed] [Google Scholar]
  34. Spignoli G., Pedata F., Pepeu G. A1 and A2 adenosine receptors modulate acetylcholine release from brain slices. Eur J Pharmacol. 1984 Jan 27;97(3-4):341–342. doi: 10.1016/0014-2999(84)90475-8. [DOI] [PubMed] [Google Scholar]
  35. Sternweis P. C., Robishaw J. D. Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J Biol Chem. 1984 Nov 25;259(22):13806–13813. [PubMed] [Google Scholar]
  36. Ukena D., Poeschla E., Hüttemann E., Schwabe U. Effects of N-ethylmaleimide on adenosine receptors of rat fat cells and human platelets. Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(3):247–253. doi: 10.1007/BF00502457. [DOI] [PubMed] [Google Scholar]
  37. Wemer J., Schoffelmeer A. N., Mulder A. H. Effects of cyclic AMP analogues and phosphodiesterase inhibitors on K+-induced [3H]noradrenaline release from rat brain slices and on its presynaptic alpha-adrenergic modulation. J Neurochem. 1982 Aug;39(2):349–356. doi: 10.1111/j.1471-4159.1982.tb03954.x. [DOI] [PubMed] [Google Scholar]
  38. Yeung S. M., Green R. D. Agonist and antagonist affinities for inhibitory adenosine receptors are reciprocally affected by 5'-guanylylimidodiphosphate or N-ethylmaleimide. J Biol Chem. 1983 Feb 25;258(4):2334–2339. [PubMed] [Google Scholar]

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

RESOURCES