Effects of Cyclic Nucleotides on the Cerebral Blood Row Response Induced by Adenosine A2B Receptor Agonist in the Rats

  • Kim, Hyun-Seung (Department of Pharmacology, College of Medicine, Hanyang University) ;
  • Shin, In-Chul (Department of Pharmacology, College of Medicine, Hanyang University)
  • 발행 : 2004.06.01

초록

This study was performed to investigate the regulatory mechanism of cerebral blood flow of adenosine $A_{2B}$ receptor agonist in the rats, and to define whether its mechanism is mediated by adenylate cyclase and guanylate cyclase. in pentobarbital-anesthetized, pentobrabital-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood How from cerebral cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine $A_{2B}$ receptor agonist, 5'-N-ethylcar-boxamidoadenosine (NECA; 4 umol/l) increased cerebral blood flow. This effect of NECA (4 umol/l) was not blocked by pretreatment with adenylate cyclase inhibitor, MDL-12330 (20 umol/l). But effect of NECA (4 umol/l) was blocked by pretreatment with guanylate cyclase inhibitor, LY-83383 (10 umol/l). These results suggest that adenosine $A_{2B}$ receptor increases cerebral blood flow. It seems that this action of adenosine $A_{2B}$ receptor is mediated via the activation of guanylate cyclase in the cerebral cortex of the rats.

키워드

참고문헌

  1. Bruns, R. F., Fergus, J. H., Badger, E. W., Bristol, J. A., Santay, L. A., Hartman, J. D., Hays, S. J. and Huang, C. C. (1987). Binding of the A$_1$-selective adenosine antagonist 8-cyclopentyl1,3- diproxylxanthine to rat brain membranes. Naunyn-Schrniedebergs Arch. Pharmacol. 335, 59-63
  2. Choca, J. I., Proudfit, H. K. and Green, R. D. (1987). Identification of A$_1$ and A$_2$ adenosine receptors in the rat spinal cord. J. Pharmacol. Exp. Ther. 242, 905-910
  3. Coney, A. M. and Marshall, J. M. (1998). Role of adenosine and its receptors in the vasodilatation induced in the cerebral cortex of the rat by systemic hypoxia. J. Physiol. 509, 507-518 https://doi.org/10.1111/j.1469-7793.1998.507bn.x
  4. Dimagl, D., Lindauer, U. and Villringer, A. (1993). Role of nitric oxide in the coupling of cerebral blood flow to neuronal activation in rats. Neurosci. Lett. 149, 43-46 https://doi.org/10.1016/0304-3940(93)90343-J
  5. Edvinsson, L. and Fredholm, B. B. (1983). Charaterization of adenosine receptors in isolated cerebral arteries of cat. Br. J. Pharmacol. 80, 631-637
  6. Feoktistov, I. and Biaggioni, I. (1997). Adenosine AlB receptors. Pharmacol. Rev. 49, 381-402
  7. Fiebich, B. L., Biber, K., Gyufko, K., Berger, M., Bauer, J. and Van-Calker, D. (1996). Adenosine Alb receptors mediate an increase in interleukin(IL)-mRNA and IL-6 protein synthesis in human astroglioma cells. J. Neurochem. 66, 1426-1431 https://doi.org/10.1046/j.1471-4159.1996.66041426.x
  8. Fredholm, B. B., Abbrachio, M. P., Bumstock, G., Daly, J. w., Harden, T. K., Jacobson, K. A., Leff, P. and Williams, M. (1994). Nomenclature and classification of purinoceptors. Pharmacol. Rev. 46, 143-156
  9. Garthwaite, J., Charles S. L. and Chess-Williams R. (1988). Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 336, 385-388 https://doi.org/10.1038/336385a0
  10. Gerber, D. and Gahwiler, B. H. (1994). GABA$_B$ and adenosine receptors mediate enhancement of the K$^+$ current, I$_A_H_P$, by reducing adenylate cyclase activity in rat CA3 hippocampal neurons. J. Neurophysiol. 72, 2360-2367
  11. Hong, K. W., Pyo, K. M., Lee, W. S., Yu, S. S and Rhim, B. Y. (1994). Pharmacological evidence that calcitonin-related peptide is implicated in cerebral autoregulation, Am. J. Heart. eirc. Physiol. 266, H11-H16
  12. Hong, K. W., Shin, H. K., Kim, H. H., Choi, J. M., Rhim, B. Y. and Lee W. S. (1999). Metabolism of exogenous cAMP to adenosine and its role for vasodilation during cerebral autoregulation in rat pial artery. Am. J. Heart. Circ. Physiol. 276, H376-H382
  13. Hong, K. W., Yoo, S. E., Yu, S. S., Lee, J. Y. and Rhim, B. Y. (1996). Pharmacological coupling and functional role for CGRP receptors in the vasodilation of rat pial arterioles, Am. J, Heart. Cire. Physiol. 270, H317-H323
  14. Hyman, A. L., Kadowitz, P. J, and Lippton, H. L. (1989). Methylene blue selectively inhibits pulmonary vasodilator responses in cats. J. Appl. Physiol. 66, 1513-1517
  15. Jiang, H., Colbran, J. L., Francis, S. H, and Corbin, J. D. (1992). Direct evidence for cross-activation of cGMP-dependent protein kinase by cAMP in pig coronary arteries. J, BioI, Chem, 267,1015-1019.
  16. Liang, B. T. and Haltiwanger, B. (1995). Adenosine A$_2_a$and A$_2_b$ receptors in cultured fetal chick heart cells. High-and lowaffinity coupling to stimulation of myocyte contractility and cAMP accumulation. Circ. Res. 76, 242-251 https://doi.org/10.1161/01.RES.76.2.242
  17. Martin, P. L. (1992). Relative agonist potencies of C2-substituted analogs of adenosine: evidence for adenosine A$_2_B$ receptors in the guinea pig aorta, Eur. J, Pharmacol. 216, 235-242
  18. Martin, P. L. and Potts, A. A. (1994). The endothelium of the rat renal artery plays an obligatory role in A$_2$ adenosine receptormediated relaxation induced by 5'-N-ethylcarboxamidoadenosine and N$^6$-cyclopentyladenosine. J. Pharmacal. Exp. Ther. 270, 893-899
  19. Mian, R. and Marshall, J, M. (1991). The role of adenosine in dilator responses induced in arterioles and venules of rat skeletal muscle by systemic hypoxia. J. Physiol. 443, 499-511
  20. Ngai, A. C. and Winn, H. R. (1993). Effects of adenosine and its analogues on isolated arterioles: extraluminal and intraluminal application. cire. Res. 73, 448-457 https://doi.org/10.1161/01.RES.73.3.448
  21. Olah, M. E. and Stiles, G. L. (1996). Adenosine receptor subtypes: characterization and therapeutic regulation. Annu. Rev. Pharmacol. Toxicol. 35, 581-606
  22. Shin, H., K., Shin, Y., W. and Hong, K., W. (2000). Role of adenosine A$_2_B$ receptors in vasodilation of rat pial artery and cerebral blood flow autoregulation. Am. J. Physiol.-Heart and Circulatory Physiology 278, H339-H344
  23. Skinner, M, R. and Marshall, J. M. (1996), Studies on the roles of ATP, adenosine and nitric oxide in mediating muscle vasodilation induced in the rat by acute systemic hypoxia. J. Physiol. 495, 553-560
  24. Stehle, J. H., Rivkees, S. A., Lee, J. J., Weaver, D. R., Deeds, J. D. and Reppert, S. M. (1992). Molecular cloning and expression of the cDNA for a novel A$_2$-adenosine receptor subtype. Mol. Endocrinol. 6, 384-393
  25. Stone, G. A., Jarvis, M. F., Sills, M. S., Weeks, B., Snowhill, E. W. and Williams, M. (1988). Species differences in high affinity adenosine A#_2$ binding sites in striatal membranes from mammalian brain. Drug Develop. Res. 15, 31-46 https://doi.org/10.1002/ddr.430150104
  26. Strohmeier, G. R., Reppert, S. M., Lencer, W. I. and Madara, J. L. (1995). The A$A_{2b}$ adenosine receptor mediates camp responses to adenosine receptor agonists in human intestinal epithelia. J. BioI. Chem, 270, 2387-2941 https://doi.org/10.1074/jbc.270.5.2387
  27. Thomas, T. and Marshall, J. M. (1994). Interdependence of respiratoryand cardiovascular changes induced by systemic hypoxia in the rat: the role of adenosine. J. Physiol. 480, 627-636
  28. Van Calker, D., Muller, M. and Hamprecht, B. (1979). Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J. Neurochem. 33, 999-1005 https://doi.org/10.1111/j.1471-4159.1979.tb05236.x
  29. Van Wylen, D. G. L., Park, T. S., Rubio, R. and Berne, R. M. (1989). The effect of local infusion of adenosine and adenosine analogues on local cerebral blood flow. J. Cereb. Blood. Flow. Metab. 9, 556-562 https://doi.org/10.1038/jcbfm.1989.79
  30. Webb, R. L., Sills, M. A., Chovan, J. P., Balwierczak, J. L. and Francis. J. E. (1992). CGS21680: a potent selective adenosine A$_2$ receptor agonist. Cardiovasc. Drug Rev. 10. 26-53.1 https://doi.org/10.1111/j.1527-3466.1992.tb00235.x
  31. Winn, H. R., Rubio, R. and Berne, R. M. (1981). The role of adenosine in the regulation of cerebral blood flow. J. Cereb. Blood. Flow. Metab. 1, 239-244 https://doi.org/10.1038/jcbfm.1981.29
  32. Wysham, D. G., Brotherton, A. F. and Heistad, D. D. (1986). Effects of forskolin on cerebral blood flow : Implications for a role of adenylate cyclase. Stroke 17, 1299-1303 https://doi.org/10.1161/01.STR.17.6.1299
  33. Zhou, H. L. and Torphy, T. J. (1991). Relationship between cyclic guanosine monophosphate accumulation and relaxation of canine trachealis induced by nitrovasodilators. J. Pharmacol. Exp. Ther. 258, 972-978