Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Oct;119(4):677–684. doi: 10.1111/j.1476-5381.1996.tb15726.x

Agmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail artery.

C González 1, S Regunathan 1, D J Reis 1, C Estrada 1
PMCID: PMC1915776  PMID: 8904641

Abstract

1. We investigated the vascular effects of agmatine (decarboxylated arginine), an endogenous ligand for alpha 2-adrenoceptors and non-adrenoceptor imidazoline (I-) receptors, present in endothelium, smooth muscle and plasma, using the rat tail artery as a model. 2. While by itself agmatine (10 nM-1 mM) was without effect on isolated arterial rings, at the highest concentration used (1 mM) it slightly increased EC50 values for contractions elicited respectively by the alpha 1- and alpha 2- adrenoceptor agonists methoxamine and clonidine. 3. Agmatine (0.03-1 mM) produced a concentration-dependent transient inhibition of the contractions induced by transmural nerve stimulation (TNS; 200 mA, 0.2 ms, 1 Hz, 10 s). This effect was abolished by the alpha 2-adrenoceptor antagonists, rawolscine and idazoxan. 4. In the presence of rawolscine or idazoxan, agmatine produced a concentration-dependent delayed facilitation of TNS-induced contractions, which was prevented by cocaine. 5. Neither inhibitory nor potentiating actions were produced by agmatine on contractions induced by noradrenaline (NA) administration. 6. Agmatine did not directly affect [3H]-NA uptake in bovine cultured chromaffin cells. 7. Agmatine can regulate vascular function by two opposing actions at sympathetic nerve terminals, with different latencies: a transient inhibition of NA release mediated by prejunctional alpha 2-adrenoceptors and a cocaine-sensitive delayed facilitation the mechanism of which is undetermined at present. 8. The results reveal the existence of a novel endogenous amine modulating NA release in the perivascular sympathetic terminals.

Full text

PDF
678

Images in this article

680Figure 2
on p.680

Selected References

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

  1. Bockman C. S., Jeffries W. B., Abel P. W. Binding and functional characterization of alpha-2 adrenergic receptor subtypes on pig vascular endothelium. J Pharmacol Exp Ther. 1993 Dec;267(3):1126–1133. [PubMed] [Google Scholar]
  2. Dyke A. C., Widdop R. E. Characterization of post-junctional alpha-adrenoceptors in the rat isolated perfused femoral artery. Eur J Pharmacol. 1987 May 7;137(1):15–23. doi: 10.1016/0014-2999(87)90177-4. [DOI] [PubMed] [Google Scholar]
  3. Ishikawa T., Misonou T., Ikeno M., Sato K., Sakamaki T. N omega-hydroxyagmatine: a novel substance causing endothelium-dependent vasorelaxation. Biochem Biophys Res Commun. 1995 Sep 5;214(1):145–151. doi: 10.1006/bbrc.1995.2268. [DOI] [PubMed] [Google Scholar]
  4. Kenigsberg R. L., Trifaró J. M. Presence of a high affinity uptake system for catecholamines in cultured bovine adrenal chromaffin cells. Neuroscience. 1980;5(9):1547–1556. doi: 10.1016/0306-4522(80)90019-6. [DOI] [PubMed] [Google Scholar]
  5. Langer S. Z., Hicks P. E. Alpha-adrenoreceptor subtypes in blood vessels: physiology and pharmacology. J Cardiovasc Pharmacol. 1984;6 (Suppl 4):S547–S558. doi: 10.1097/00005344-198406004-00001. [DOI] [PubMed] [Google Scholar]
  6. Li G., Regunathan S., Barrow C. J., Eshraghi J., Cooper R., Reis D. J. Agmatine: an endogenous clonidine-displacing substance in the brain. Science. 1994 Feb 18;263(5149):966–969. doi: 10.1126/science.7906055. [DOI] [PubMed] [Google Scholar]
  7. Livett B. G. Adrenal medullary chromaffin cells in vitro. Physiol Rev. 1984 Oct;64(4):1103–1161. doi: 10.1152/physrev.1984.64.4.1103. [DOI] [PubMed] [Google Scholar]
  8. Medgett I. C., Langer S. Z. Heterogeneity of smooth muscle alpha adrenoceptors in rat tail artery in vitro. J Pharmacol Exp Ther. 1984 Jun;229(3):823–830. [PubMed] [Google Scholar]
  9. Molderings G. J., Göthert M. Inhibitory presynaptic imidazoline receptors on sympathetic nerves in the rabbit aorta differ from I1- and I2-imidazoline binding sites. Naunyn Schmiedebergs Arch Pharmacol. 1995 May;351(5):507–516. doi: 10.1007/BF00171042. [DOI] [PubMed] [Google Scholar]
  10. Molderings G. J., Hentrich F., Göthert M. Pharmacological characterization of the imidazoline receptor which mediates inhibition of noradrenaline release in the rabbit pulmonary artery. Naunyn Schmiedebergs Arch Pharmacol. 1991 Dec;344(6):630–638. doi: 10.1007/BF00174746. [DOI] [PubMed] [Google Scholar]
  11. Moro M. A., López M. G., Gandía L., Michelena P., García A. G. Separation and culture of living adrenaline- and noradrenaline-containing cells from bovine adrenal medullae. Anal Biochem. 1990 Mar;185(2):243–248. doi: 10.1016/0003-2697(90)90287-j. [DOI] [PubMed] [Google Scholar]
  12. Piletz J. E., Chikkala D. N., Ernsberger P. Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. J Pharmacol Exp Ther. 1995 Feb;272(2):581–587. [PubMed] [Google Scholar]
  13. Pinthong D., Wright I. K., Hanmer C., Millns P., Mason R., Kendall D. A., Wilson V. G. Agmatine recognizes alpha 2-adrenoceptor binding sites but neither activates nor inhibits alpha 2-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1995 Jan;351(1):10–16. doi: 10.1007/BF00169058. [DOI] [PubMed] [Google Scholar]
  14. Raasch W., Regunathan S., Li G., Reis D. J. Agmatine, the bacterial amine, is widely distributed in mammalian tissues. Life Sci. 1995;56(26):2319–2330. doi: 10.1016/0024-3205(95)00226-v. [DOI] [PubMed] [Google Scholar]
  15. Regunathan S., Reis D. J. Imidazoline receptors and their endogenous ligands. Annu Rev Pharmacol Toxicol. 1996;36:511–544. doi: 10.1146/annurev.pa.36.040196.002455. [DOI] [PubMed] [Google Scholar]
  16. Regunathan S., Youngson C., Raasch W., Wang H., Reis D. J. Imidazoline receptors and agmatine in blood vessels: a novel system inhibiting vascular smooth muscle proliferation. J Pharmacol Exp Ther. 1996 Mar;276(3):1272–1282. [PubMed] [Google Scholar]
  17. Reis D. J., Li G., Regunathan S. Endogenous ligands of imidazoline receptors: classic and immunoreactive clonidine-displacing substance and agmatine. Ann N Y Acad Sci. 1995 Jul 12;763:295–313. doi: 10.1111/j.1749-6632.1995.tb32416.x. [DOI] [PubMed] [Google Scholar]
  18. Tabor C. W., Tabor H. Polyamines. Annu Rev Biochem. 1984;53:749–790. doi: 10.1146/annurev.bi.53.070184.003533. [DOI] [PubMed] [Google Scholar]
  19. Xiao X. H., Rand M. J. Alpha 2-adrenoceptor agonists enhance vasoconstrictor responses to alpha 1-adrenoceptor agonists in the rat tail artery by increasing the influx of Ca2+. Br J Pharmacol. 1989 Nov;98(3):1032–1038. doi: 10.1111/j.1476-5381.1989.tb14635.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES