Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1997 Apr;6(2):141–145. doi: 10.1080/09629359791848

Mast cell amines and inosineinduced vasoconstriction in the rat hind limb

A M Northover 1,✉, B J Northover 1
PMCID: PMC2365850  PMID: 18472848

Abstract

Under certain circumstances injected inosine causes a net vasoconstrictive effect on the arterioles, which has been attributed to 5-hydroxytryptamine (5HT) released in response to adenosine type 3 (A3) receptor stimulation of mast cells residing in the adventitia. We have sought further evidence for this hypothesis using blood vessels of the rat hind limb perfused in vitro at constant rate with a gelatin-containing physiological salt solution. Injection of inosine (2.7 mg) caused a rise in perfusion pressure, which was only slightly increased by inclusion of N-nitro-L-arginine methyl ester (100 μM) in the perfusate. Inclusion in the perfusate of cyproheptadine (1 μM), compound 48 80 (1 μg ml), 8-phenyltheophylline (1 μM) or 8-cyclopentyl-1,3 dipropylxanthine (0.1 μM) greatly reduced the pressor response to inosine. The pressor effect of injected 5HT (400 μg) was abolished by pre-treatment with cyproheptadine, but not by pre-treatment with compound 48 80. These results suggest that the net pressor response to injected inosine was mainly the result of an A1 receptor-mediated release of 5HT, most probably from mast cells. No evidence was found for an involvement of A3 receptor stimulation.

Full Text

The Full Text of this article is available as a PDF (201.3 KB).

Selected References

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

  1. Brown C. M., Collis M. G. Adenosine contracts the isolated rat tail artery by releasing endogenous 5-hydroxytryptamine. Eur J Pharmacol. 1981 Dec 3;76(2-3):275–277. doi: 10.1016/0014-2999(81)90513-6. [DOI] [PubMed] [Google Scholar]
  2. Bruns R. F., Fergus J. H., Badger E. W., Bristol J. A., Santay L. A., Hartman J. D., Hays S. J., Huang C. C. Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes. Naunyn Schmiedebergs Arch Pharmacol. 1987 Jan;335(1):59–63. doi: 10.1007/BF00165037. [DOI] [PubMed] [Google Scholar]
  3. Burnstock G., Lincoln J., Fehér E., Hopwood A. M., Kirkpatrick K., Milner P., Ralevic V. Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: a possible new mechanism for hypoxia-induced vasodilatation of the rat heart. Experientia. 1988 Aug 15;44(8):705–707. doi: 10.1007/BF01941035. [DOI] [PubMed] [Google Scholar]
  4. Church M. K., Hughes P. J., Vardey C. J. Studies on the receptor mediating cyclic AMP-independent enhancement by adenosine of IgE-dependent mediator release from rat mast cells. Br J Pharmacol. 1986 Jan;87(1):233–242. doi: 10.1111/j.1476-5381.1986.tb10176.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Daly J. W. Adenosine receptors: targets for future drugs. J Med Chem. 1982 Mar;25(3):197–207. doi: 10.1021/jm00345a001. [DOI] [PubMed] [Google Scholar]
  6. Dart C., Standen N. B. Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery. J Physiol. 1993 Nov;471:767–786. doi: 10.1113/jphysiol.1993.sp019927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dobson J. G., Jr, Rubio R., Berne R. M. Role of adenine nucleotides, adenosine, and inorganic phosphate in the regulation of skeletal muscle blood flow. Circ Res. 1971 Oct;29(4):375–384. doi: 10.1161/01.res.29.4.375. [DOI] [PubMed] [Google Scholar]
  8. Doyle M. P., Linden J., Duling B. R. Nucleoside-induced arteriolar constriction: a mast cell-dependent response. Am J Physiol. 1994 May;266(5 Pt 2):H2042–H2050. doi: 10.1152/ajpheart.1994.266.5.H2042. [DOI] [PubMed] [Google Scholar]
  9. Fozard J. R., Pfannkuche H. J., Schuurman H. J. Mast cell degranulation following adenosine A3 receptor activation in rats. Eur J Pharmacol. 1996 Mar 18;298(3):293–297. doi: 10.1016/0014-2999(95)00822-5. [DOI] [PubMed] [Google Scholar]
  10. GLOVER W. E., MARSHALL R. J., WHELAN R. F. The antagonism of the vascular effects of 5-hydroxytryptamine by BOL 148 and sodium salicylate in the human subject. Br J Pharmacol Chemother. 1957 Dec;12(4):498–503. doi: 10.1111/j.1476-5381.1957.tb00172.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gallo-Rodriguez C., Ji X. D., Melman N., Siegman B. D., Sanders L. H., Orlina J., Fischer B., Pu Q., Olah M. E., van Galen P. J. Structure-activity relationships of N6-benzyladenosine-5'-uronamides as A3-selective adenosine agonists. J Med Chem. 1994 Mar 4;37(5):636–646. doi: 10.1021/jm00031a014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haddy F. J., Scott J. B. Metabolically linked vasoactive chemicals in local regulation of blood flow. Physiol Rev. 1968 Oct;48(4):688–707. doi: 10.1152/physrev.1968.48.4.688. [DOI] [PubMed] [Google Scholar]
  13. Hamilton H. W., Taylor M. D., Steffen R. P., Haleen S. J., Bruns R. F. Correlation of adenosine receptor affinities and cardiovascular activity. Life Sci. 1987 Nov 16;41(20):2295–2302. doi: 10.1016/0024-3205(87)90542-x. [DOI] [PubMed] [Google Scholar]
  14. Hughes P. J., Holgate S. T., Church M. K. Adenosine inhibits and potentiates IgE-dependent histamine release from human lung mast cells by an A2-purinoceptor mediated mechanism. Biochem Pharmacol. 1984 Dec 1;33(23):3847–3852. doi: 10.1016/0006-2952(84)90050-9. [DOI] [PubMed] [Google Scholar]
  15. JACOB M. I., BERNE R. M. Metabolism of purine derivatives by the isolated cat heart. Am J Physiol. 1960 Feb;198:322–326. doi: 10.1152/ajplegacy.1960.198.2.322. [DOI] [PubMed] [Google Scholar]
  16. Jones C. E., Mayer L. R. Nonmetabolically coupled coronary vasodilatation during inosine infusion in dogs. Am J Physiol. 1980 Apr;238(4):H569–H574. doi: 10.1152/ajpheart.1980.238.4.H569. [DOI] [PubMed] [Google Scholar]
  17. Kurachi Y. G protein regulation of cardiac muscarinic potassium channel. Am J Physiol. 1995 Oct;269(4 Pt 1):C821–C830. doi: 10.1152/ajpcell.1995.269.4.C821. [DOI] [PubMed] [Google Scholar]
  18. Lohse M. J., Maurer K., Gensheimer H. P., Schwabe U. Dual actions of adenosine on rat peritoneal mast cells. Naunyn Schmiedebergs Arch Pharmacol. 1987 May;335(5):555–560. doi: 10.1007/BF00169124. [DOI] [PubMed] [Google Scholar]
  19. Marquardt D. L., Parker C. W., Sullivan T. J. Potentiation of mast cell mediator release by adenosine. J Immunol. 1978 Mar;120(3):871–878. [PubMed] [Google Scholar]
  20. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  21. Northover A. M., Northover B. J. Degranulation of rat omental mast cells by A(1) receptor agonists in vitro. Mediators Inflamm. 1996;5(5):341–345. doi: 10.1155/S096293519600049X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Prentice D. J., Hourani S. M. Activation of multiple sites by adenosine analogues in the rat isolated aorta. Br J Pharmacol. 1996 Jul;118(6):1509–1517. doi: 10.1111/j.1476-5381.1996.tb15567.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ramkumar V., Stiles G. L., Beaven M. A., Ali H. The A3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells. J Biol Chem. 1993 Aug 15;268(23):16887–16890. [PubMed] [Google Scholar]
  24. Raud J., Dahlén S. E., Smedegård G., Hedqvist P. An intravital microscopic model for mast cell-dependent inflammation in the hamster cheek pouch. Acta Physiol Scand. 1989 Feb;135(2):95–105. doi: 10.1111/j.1748-1716.1989.tb08556.x. [DOI] [PubMed] [Google Scholar]
  25. Rees D. D., Palmer R. M., Schulz R., Hodson H. F., Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990 Nov;101(3):746–752. doi: 10.1111/j.1476-5381.1990.tb14151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rubio R., Berne R. M., Katori M. Release of adenosine in reactive hyperemia of the dog heart. Am J Physiol. 1969 Jan;216(1):56–62. doi: 10.1152/ajplegacy.1969.216.1.56. [DOI] [PubMed] [Google Scholar]
  27. SANYAL R. K., WEST G. B. THE ROLE OF HISTAMINE AND 5-HYDROXYTRYPTAMINE IN INJURY. Int Arch Allergy Appl Immunol. 1965;26:362–372. doi: 10.1159/000229590. [DOI] [PubMed] [Google Scholar]
  28. Sakai K., Akima M., Matsushita H. Femoral vascular responses to purine and pyrimidine derivatives: release of 5-hydroxytryptamine by purine derivatives in isolated, cross-circulated rat hindlimb. Jpn J Pharmacol. 1979 Apr;29(2):243–251. doi: 10.1254/jjp.29.243. [DOI] [PubMed] [Google Scholar]
  29. Sakai K., Akima M. Vasoconstriction after adenosine and inosine in the rat isolated hindlimb abolished by blockade of tryptaminergic mechanisms. Naunyn Schmiedebergs Arch Pharmacol. 1978 Mar;302(1):55–59. doi: 10.1007/BF00586597. [DOI] [PubMed] [Google Scholar]
  30. Selye H., Somogyi A. Effect of cyproheptadine upon acute inflammation produced by various agents. Med Pharmacol Exp Int J Exp Med. 1967;17(3):255–263. doi: 10.1159/000137084. [DOI] [PubMed] [Google Scholar]
  31. Shepherd R. K., Duling B. R. Inosine-induced vasoconstriction is mediated by histamine and thromboxane derived from mast cells. Am J Physiol. 1996 Feb;270(2 Pt 2):H560–H566. doi: 10.1152/ajpheart.1996.270.2.H560. [DOI] [PubMed] [Google Scholar]
  32. Shepherd R. K., Linden J., Duling B. R. Adenosine-induced vasoconstriction in vivo. Role of the mast cell and A3 adenosine receptor. Circ Res. 1996 Apr;78(4):627–634. doi: 10.1161/01.res.78.4.627. [DOI] [PubMed] [Google Scholar]
  33. Yang B. C., Mehta J. L. Platelets increase the tone of quiescent rat aortic rings by release of serotonin and potentiate the subsequent contractile response to norepinephrine. J Cardiovasc Pharmacol. 1994 Mar;23(3):387–394. [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES