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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Feb;90(2):383–391. doi: 10.1111/j.1476-5381.1987.tb08968.x

P2-purinoceptors of two subtypes in the rabbit mesenteric artery: reactive blue 2 selectively inhibits responses mediated via the P2y-but not the P2x-purinoceptor.

G Burnstock, J J Warland
PMCID: PMC1916939  PMID: 3828656

Abstract

alpha,beta-Methylene ATP and ATP both produced concentration-dependent contractions of the isolated mesenteric artery of the rabbit that were not inhibited by reactive blue 2. In preparations where the tone had been raised with noradrenaline, ATP and 2-methylthio ATP, but not alpha,beta-methylene ATP, produced relaxations of the vessel. These relaxations were inhibited in the presence of reactive blue 2. Reactive blue 2 did not inhibit the contractions to noradrenaline, and only slightly inhibited relaxations to adenosine and acetylcholine. The rank order of potency of purine nucleotide analogues in contracting the vessel was: alpha,beta-methylene ATP greater than beta,gamma-methylene ATP = 2-methylthio ATP greater than ATP, and in relaxing the vessel at raised tone was: 2-methylthio ATP greater than ATP greater than beta,gamma-methylene ATP greater than alpha,beta-methylene ATP. It is concluded from this study that in the isolated mesenteric artery of the rabbit, purine nucleotides act via P2y-purinoceptors to cause the muscle to relax and via P2x-purinoceptors to cause the muscle to contract. The results also suggest that reactive blue 2 selectively inhibits responses mediated via the P2y-purinoceptor, at least within a limited concentration range.

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Selected References

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  1. BULBRING E. Measurements of oxygen consumption in smooth muscle. J Physiol. 1953 Oct;122(1):111–134. doi: 10.1113/jphysiol.1953.sp004983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevan J. A., Osher J. V. A direct method for recording tension changes in the wall of small blood vessels in vitro. Agents Actions. 1972;2(5):257–260. doi: 10.1007/BF02087051. [DOI] [PubMed] [Google Scholar]
  3. Brown C., Burnstock G., Cocks T. Effects of adenosine 5'-triphosphate (ATP) and beta-gamma-methylene ATP on the rat urinary bladder. Br J Pharmacol. 1979 Jan;65(1):97–102. doi: 10.1111/j.1476-5381.1979.tb17337.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burnstock G., Cusack N. J., Hills J. M., MacKenzie I., Meghji P. Studies on the stereoselectivity of the P2-purinoceptor. Br J Pharmacol. 1983 Aug;79(4):907–913. doi: 10.1111/j.1476-5381.1983.tb10535.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burnstock G., Cusack N. J., Meldrum L. A. Studies on the stereoselectivity of the P2-purinoceptor on the guinea-pig vas deferens. Br J Pharmacol. 1985 Feb;84(2):431–434. doi: 10.1111/j.1476-5381.1985.tb12927.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burnstock G., Kennedy C. Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol. 1985;16(5):433–440. doi: 10.1016/0306-3623(85)90001-1. [DOI] [PubMed] [Google Scholar]
  7. Chapal J., Loubatieres-Mariani M. M. Evidence for purinergic receptors on vascular smooth muscle in rat pancreas. Eur J Pharmacol. 1983 Mar 4;87(4):423–430. doi: 10.1016/0014-2999(83)90081-x. [DOI] [PubMed] [Google Scholar]
  8. Choo L. K. The effect of reactive blue, an antagonist of ATP, on the isolated urinary bladders of guinea-pig and rat. J Pharm Pharmacol. 1981 Apr;33(4):248–250. doi: 10.1111/j.2042-7158.1981.tb13770.x. [DOI] [PubMed] [Google Scholar]
  9. Crema A., Frigo G. M., Lecchini S., Manzo L., Onori L., Tonini M. Purine receptors in the guinea-pig internal anal sphincter. Br J Pharmacol. 1983 Mar;78(3):599–603. doi: 10.1111/j.1476-5381.1983.tb08820.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cusack N. J., Pearson J. D., Gordon J. L. Stereoselectivity of ectonucleotidases on vascular endothelial cells. Biochem J. 1983 Sep 15;214(3):975–981. doi: 10.1042/bj2140975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fedan J. S., Hogaboom G. K., Westfall D. P., O'Donnell J. P. Comparison of contractions of the smooth muscle of the guinea-pig vas deferens induced by ATP and related nucleotides. Eur J Pharmacol. 1982 Jul 9;81(2):193–204. doi: 10.1016/0014-2999(82)90437-x. [DOI] [PubMed] [Google Scholar]
  12. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  13. Gruetter C. A., Gruetter D. Y., Lyon J. E., Kadowitz P. J., Ignarro L. J. Relationship between cyclic guanosine 3':5'-monophosphate formation and relaxation of coronary arterial smooth muscle by glyceryl trinitrate, nitroprusside, nitrite and nitric oxide: effects of methylene blue and methemoglobin. J Pharmacol Exp Ther. 1981 Oct;219(1):181–186. [PubMed] [Google Scholar]
  14. Hogaboom G. K., O'Donnell J. P., Fedan J. S. Purinergic receptors: photoaffinity analog of adenosine triphosphate is a specific adenosine triphosphate antagonist. Science. 1980 Jun 13;208(4449):1273–1276. doi: 10.1126/science.6103581. [DOI] [PubMed] [Google Scholar]
  15. Kasakov L., Burnstock G. The use of the slowly degradable analog, alpha, beta-methylene ATP, to produce desensitisation of the P2-purinoceptor: effect on non-adrenergic, non-cholinergic responses of the guinea-pig urinary bladder. Eur J Pharmacol. 1982 Dec 24;86(2):291–294. doi: 10.1016/0014-2999(82)90330-2. [DOI] [PubMed] [Google Scholar]
  16. Kennedy C., Burnstock G. ATP produces vasodilation via P1 purinoceptors and vasoconstriction via P2 purinoceptors in the isolated rabbit central ear artery. Blood Vessels. 1985;22(3):145–155. doi: 10.1159/000158592. [DOI] [PubMed] [Google Scholar]
  17. Kennedy C., Burnstock G. Evidence for two types of P2-purinoceptor in longitudinal muscle of the rabbit portal vein. Eur J Pharmacol. 1985 Apr 23;111(1):49–56. doi: 10.1016/0014-2999(85)90112-8. [DOI] [PubMed] [Google Scholar]
  18. Kennedy C., Delbro D., Burnstock G. P2-purinoceptors mediate both vasodilation (via the endothelium) and vasoconstriction of the isolated rat femoral artery. Eur J Pharmacol. 1985 Jan 2;107(2):161–168. doi: 10.1016/0014-2999(85)90055-x. [DOI] [PubMed] [Google Scholar]
  19. Maguire M. H., Satchell D. G. The contribution of adenosine to the inhibitory actions of adenine nucleotides on the guinea-pig taenia coli: studies with phosphate-modified adenine nucleotide analogs and dipyridamole. J Pharmacol Exp Ther. 1979 Dec;211(3):626–631. [PubMed] [Google Scholar]
  20. Manzini S., Hoyle C. H., Burnstock G. An electrophysiological analysis of the effect of reactive blue 2, a putative P2-purinoceptor antagonist, on inhibitory junction potentials of rat caecum. Eur J Pharmacol. 1986 Aug 15;127(3):197–204. doi: 10.1016/0014-2999(86)90364-x. [DOI] [PubMed] [Google Scholar]
  21. Manzini S., Maggi C. A., Meli A. Further evidence for involvement of adenosine-5'-triphosphate in non-adrenergic non-cholinergic relaxation of the isolated rat duodenum. Eur J Pharmacol. 1985 Jul 31;113(3):399–408. doi: 10.1016/0014-2999(85)90088-3. [DOI] [PubMed] [Google Scholar]
  22. Martin W., Cusack N. J., Carleton J. S., Gordon J. L. Specificity of P2-purinoceptor that mediates endothelium-dependent relaxation of the pig aorta. Eur J Pharmacol. 1985 Feb 5;108(3):295–299. doi: 10.1016/0014-2999(85)90452-2. [DOI] [PubMed] [Google Scholar]
  23. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  24. Mathieson J. J., Burnstock G. Purine-mediated relaxation and constriction of isolated rabbit mesenteric artery are not endothelium-dependent. Eur J Pharmacol. 1985 Dec 3;118(3):221–229. doi: 10.1016/0014-2999(85)90132-3. [DOI] [PubMed] [Google Scholar]
  25. Moody C. J., Burnstock G. Evidence for the presence of P1-purinoceptors on cholinergic nerve terminals in the guinea-pig ileum. Eur J Pharmacol. 1982 Jan 8;77(1):1–9. doi: 10.1016/0014-2999(82)90527-1. [DOI] [PubMed] [Google Scholar]
  26. Pearson J. D., Cusack N. J. Investigation of the preferred Mg(II)-adenine-nucleotide complex at the active site of ectonucleotidases in intact vascular cells using phosphorothioate analogues of ADP and ATP. Eur J Biochem. 1985 Sep 2;151(2):373–375. doi: 10.1111/j.1432-1033.1985.tb09111.x. [DOI] [PubMed] [Google Scholar]
  27. Satchell D. G., Maguire M. H. Inhibitory effects of adenine nucleotide analogs on the isolated guinea-pig taenia coli. J Pharmacol Exp Ther. 1975 Dec;195(3):540–548. [PubMed] [Google Scholar]
  28. Vanhoutte P. M., Rimele T. J. Role of the endothelium in the control of vascular smooth muscle function. J Physiol (Paris) 1982;78(7):681–686. [PubMed] [Google Scholar]
  29. Weber B. H., Willeford K., Moe J. G., Piszkiewicz D. Hazards in the use of Cibacron Blue F3GA in studies of proteins. Biochem Biophys Res Commun. 1979 Jan 30;86(2):252–258. doi: 10.1016/0006-291x(79)90859-3. [DOI] [PubMed] [Google Scholar]
  30. White T. D., Chaudhry A., Vohra M. M., Webb D., Leslie R. A. Characteristics of P2 (nucleotide) receptors mediating contraction and relaxation of rat aortic strips: possible physiological relevance. Eur J Pharmacol. 1985 Nov 26;118(1-2):37–44. doi: 10.1016/0014-2999(85)90660-0. [DOI] [PubMed] [Google Scholar]

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