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. 1992 Aug;106(4):871–876. doi: 10.1111/j.1476-5381.1992.tb14427.x

Prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are sensitive to N-ethylmaleimide, but not pertussis toxin.

T V Murphy 1, S Foucart 1, H Majewski 1
PMCID: PMC1907645  PMID: 1356569

Abstract

1. The identity of the G-proteins involved in prejunctional alpha 2-adrenoceptor signal transduction in mouse atria was examined by use of the G-protein inactivators N-ethylmaleimide and pertussis toxin. 2. The alpha 2-adrenoceptor partial agonist clonidine (0.03 microM) inhibited the electrical stimulation-induced (S-I) outflow of radioactivity from mouse atria which were incubated with [3H]-noradrenaline and stimulated at 5 Hz. The partial alpha 2-adrenoceptor agonist St 363 (10 microM) inhibited the S-I outflow of radioactivity at the lower stimulation frequency of 2.5 Hz. The inhibitory effects of these compounds were not altered in mice pretreated with pertussis toxin (1.5 micrograms, i.v.). 3. The alpha 2-adrenoceptor antagonist, idazoxan (0.1 microM), increased the S-I outflow of radioactivity from mouse atria stimulated at 5 Hz, and this effect was not altered in atria from mice pretreated with pertussis toxin. 4. The inhibitory effects of clonidine and St 363 and the facilitatory effect of idazoxan on the S-I outflow of radioactivity from mouse atria were significantly less in atria incubated with N-ethylmaleimide (NEM, 3 microM) for 60 min before the [3H]-noradrenaline incubation. 5. The results suggest that prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are NEM-sensitive, but pertussis toxin insensitive.

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Selected References

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  1. 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]
  2. 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]
  3. Boyer J. L., Cárdenas C., Posadas C., García-Sáinz J. A. "Pertussis toxin induces tachycardia and impairs the increase in blood pressure produced by alpha 2-adrenergic agonists". Life Sci. 1983 Dec 26;33(26):2627–2633. doi: 10.1016/0024-3205(83)90346-6. [DOI] [PubMed] [Google Scholar]
  4. Docherty J. R. No effect of pertussis toxin on peripheral prejunctional alpha 2-adrenoceptor-mediated responses and on endothelium-dependent relaxations in the rat. Br J Pharmacol. 1990 Jun;100(2):348–352. doi: 10.1111/j.1476-5381.1990.tb15807.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Docherty J. R. Pertussis toxin and pre-junctional alpha 2-adrenoreceptors in rat heart and vas deferens. J Auton Pharmacol. 1988 Sep;8(3):197–201. doi: 10.1111/j.1474-8673.1988.tb00183.x. [DOI] [PubMed] [Google Scholar]
  6. Foucart S., Murphy T. V., Majewski H. Prejunctional beta-adrenoceptors, angiotensin II and neuropeptide Y receptors on sympathetic nerves in mouse atria are linked to N-ethylmaleimide-susceptible G-proteins. J Auton Nerv Syst. 1990 Jul;30(3):221–232. doi: 10.1016/0165-1838(90)90253-f. [DOI] [PubMed] [Google Scholar]
  7. Harrison J. K., Pearson W. R., Lynch K. R. Molecular characterization of alpha 1- and alpha 2-adrenoceptors. Trends Pharmacol Sci. 1991 Feb;12(2):62–67. doi: 10.1016/0165-6147(91)90499-i. [DOI] [PubMed] [Google Scholar]
  8. Hertting G., Allgaier C. Participation of protein kinase C and regulatory G proteins in modulation of the evoked noradrenaline release in brain. Cell Mol Neurobiol. 1988 Mar;8(1):105–114. doi: 10.1007/BF00712916. [DOI] [PubMed] [Google Scholar]
  9. Illes P., Weber H. D., Neuburger J., Bucher B., Regenold J. T., Nörenberg W. Receptor interactions at noradrenergic neurones. Ann N Y Acad Sci. 1990;604:197–210. doi: 10.1111/j.1749-6632.1990.tb31994.x. [DOI] [PubMed] [Google Scholar]
  10. Kaschube M., Brasch H. Pre- and postjunctional effects of N-ethylmaleimide in the isolated mouse vas deferens. Eur J Pharmacol. 1990 Mar 20;178(2):151–159. doi: 10.1016/0014-2999(90)90470-q. [DOI] [PubMed] [Google Scholar]
  11. Katada T., Ui M. In vitro effects of islet-activating protein on cultured rat pancreatic islets. Enhancement of insulin secretion, adenosine 3':5'-monophosphate accumulation and 45Ca flux. J Biochem. 1981 Apr;89(4):979–990. [PubMed] [Google Scholar]
  12. Kitamura Y., Nomura Y. Uncoupling of rat cerebral cortical alpha 2-adrenoceptors from GTP-binding proteins by N-ethylmaleimide. J Neurochem. 1987 Dec;49(6):1894–1901. doi: 10.1111/j.1471-4159.1987.tb02452.x. [DOI] [PubMed] [Google Scholar]
  13. Lai R. T., Watanabe Y., Yoshida H. Effect of islet-activating protein (IAP) on contractile responses of rat vas deferens: evidence for participation of Ni (inhibitory GTP binding regulating protein) in the alpha 2-adrenoceptor-mediated response. Eur J Pharmacol. 1983 Jun 17;90(4):453–456. doi: 10.1016/0014-2999(83)90572-1. [DOI] [PubMed] [Google Scholar]
  14. Lux B., Schulz R. Effect of cholera toxin and pertussis toxin on opioid tolerance and dependence in the guinea-pig myenteric plexus. J Pharmacol Exp Ther. 1986 Jun;237(3):995–1000. [PubMed] [Google Scholar]
  15. Martin J. M., Hunter D. D., Nathanson N. M. Islet activating protein inhibits physiological responses evoked by cardiac muscarinic acetylcholine receptors. Role of guanosine triphosphate binding proteins in regulation of potassium permeability. Biochemistry. 1985 Dec 17;24(26):7521–7525. doi: 10.1021/bi00347a003. [DOI] [PubMed] [Google Scholar]
  16. Medgett I. C., McCulloch M. W., Rand M. J. Partial agonist of clonidine on prejunctional and postjunctional alpha-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1978 Oct;304(3):215–221. doi: 10.1007/BF00507961. [DOI] [PubMed] [Google Scholar]
  17. Medgett I. C., McCulloch M. W. Receptor sites of action of clonidine: effects of clonidine and three structural isomers on prejunctional and postjunctional alpha-adrenoceptors and histamine H2-receptors in guinea-pig isolated cardiovascular tissues. J Pharm Pharmacol. 1980 Feb;32(2):137–138. doi: 10.1111/j.2042-7158.1980.tb12871.x. [DOI] [PubMed] [Google Scholar]
  18. Murphy T. V., Majewski H. Pertussis toxin differentiates between alpha 1- and alpha 2-adrenoceptor-mediated inhibition of noradrenaline release from rat kidney cortex. Eur J Pharmacol. 1990 Apr 25;179(3):435–439. doi: 10.1016/0014-2999(90)90185-9. [DOI] [PubMed] [Google Scholar]
  19. Musgrave I., Marley P., Majewski H. Pertussis toxin does not attenuate alpha 2-adrenoceptor mediated inhibition of noradrenaline release in mouse atria. Naunyn Schmiedebergs Arch Pharmacol. 1987 Sep;336(3):280–286. doi: 10.1007/BF00172679. [DOI] [PubMed] [Google Scholar]
  20. Nichols A. J., Motley E. D., Ruffolo R. R., Jr Differential effect of pertussis toxin on pre- and postjunctional alpha 2-adrenoceptors in the cardiovascular system of the pithed rat. Eur J Pharmacol. 1988 Jan 19;145(3):345–349. doi: 10.1016/0014-2999(88)90440-2. [DOI] [PubMed] [Google Scholar]
  21. Nozaki M., Sperelakis N. Pertussis toxin effects on transmitter release from perivascular nerve terminals. Am J Physiol. 1989 Feb;256(2 Pt 2):H455–H459. doi: 10.1152/ajpheart.1989.256.2.H455. [DOI] [PubMed] [Google Scholar]
  22. Pobiner B. F., Hewlett E. L., Garrison J. C. Role of Ni in coupling angiotensin receptors to inhibition of adenylate cyclase in hepatocytes. J Biol Chem. 1985 Dec 25;260(30):16200–16209. [PubMed] [Google Scholar]
  23. Rump L. C., Majewski H. Modulation of norepinephrine release through alpha 1- and alpha 2-adrenoceptors in rat isolated kidney. J Cardiovasc Pharmacol. 1987 Apr;9(4):500–507. doi: 10.1097/00005344-198704000-00016. [DOI] [PubMed] [Google Scholar]
  24. Sabatini S., Kurtzman N. A. Vanadate stimulates the N-ethylmaleimide-sensitive adenosine triphosphatase in rat nephron. J Pharmacol Exp Ther. 1989 Aug;250(2):529–533. [PubMed] [Google Scholar]
  25. Schömig E., Michael-Hepp J., Bönisch H. Inhibition of neuronal noradrenaline uptake (uptake1) and desipramine binding by N-ethylmaleimide (NEM). Naunyn Schmiedebergs Arch Pharmacol. 1988 Jun;337(6):633–636. doi: 10.1007/BF00175788. [DOI] [PubMed] [Google Scholar]
  26. Sigafoos J. F., Abramowitz J. Effects of N-ethylmaleimide on gonadotropin and beta-adrenergic receptor function coupled to rabbit luteal adenylyl cyclase. Endocrinology. 1986 Oct;119(4):1432–1438. doi: 10.1210/endo-119-4-1432. [DOI] [PubMed] [Google Scholar]
  27. Smith D. K., Lauf P. K. Effects of N-ethylmaleimide on ouabain-insensitive cation fluxes in human red cell ghosts. Biochim Biophys Acta. 1985 Aug 27;818(2):251–259. doi: 10.1016/0005-2736(85)90565-6. [DOI] [PubMed] [Google Scholar]
  28. Starke K. Presynaptic alpha-autoreceptors. Rev Physiol Biochem Pharmacol. 1987;107:73–146. [PubMed] [Google Scholar]
  29. Starke K. Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol. 1977;77:1–124. doi: 10.1007/BFb0050157. [DOI] [PubMed] [Google Scholar]
  30. Ueda H., Misawa H., Katada T., Ui M., Takagi H., Satoh M. Functional reconstruction of purified Gi and Go with mu-opioid receptors in guinea pig striatal membranes pretreated with micromolar concentrations of N-ethylmaleimide. J Neurochem. 1990 Mar;54(3):841–848. doi: 10.1111/j.1471-4159.1990.tb02328.x. [DOI] [PubMed] [Google Scholar]
  31. Winslow J. W., Bradley J. D., Smith J. A., Neer E. J. Reactive sulfhydryl groups of alpha 39, a guanine nucleotide-binding protein from brain. Location and function. J Biol Chem. 1987 Apr 5;262(10):4501–4507. [PubMed] [Google Scholar]
  32. Wölfel R., Halbrügge T., Graefe K. H. Effects of N-ethylmaleimide on 5-hydroxytryptamine transport and sodium content in rabbit platelets. Br J Pharmacol. 1989 Aug;97(4):1308–1314. doi: 10.1111/j.1476-5381.1989.tb12593.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zeng D. W., Harrison J. K., D'Angelo D. D., Barber C. M., Tucker A. L., Lu Z. H., Lynch K. R. Molecular characterization of a rat alpha 2B-adrenergic receptor. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3102–3106. doi: 10.1073/pnas.87.8.3102. [DOI] [PMC free article] [PubMed] [Google Scholar]

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