Browse > Article

The Regulatory Mechanism of Cerebral Blood How of Adenosine A2 Receptor Agonist in the Rats  

Kang, Hyung-Kil (Department of Pharmacology, College of Medicine, Hanyang University)
Shin, In-Chul (Department of Pharmacology, College of Medicine, Hanyang University)
Publication Information
Biomolecules & Therapeutics / v.12, no.2, 2004 , pp. 68-73 More about this Journal
Abstract
This study was performed to investigate the regulatory mechanism of cerebral blood How of adenosine $A_2$ receptor agonist in the rats, and to define whether its mechanism is mediated by nitric oxide (NO), adenylate cyclase and guanylate cyclase. In pentobarbital-anesthetized, pancuronium-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood flow from cerebal cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine $A_2$ receptor agonist [5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 4 umol/l)] increased cerebral blood flow. This effect of CPCA (4 umol/l) was blocked by pretreatment with NO synthase inhibitor [$N^G$-nitro-L-argine methylester (L-NAME; 140 umol/l)] and adenylate cyclase inhibitor [MDL-12,330 (20 umol/l)]. But the effect of CPCA (4 umol/l) was not blocked by pretreatment with guanylate cyclase inhibitor [LY-83,583 (10 umol/l)]. These results suggest that adenosine $A_2$ receptor increases cerebral blood How. It seems that this action of adenosine $A_2$ receptor is mediated via the NO and the activation of adenylate cyclase in the cerebral cortex of the rats.
Keywords
adenosine; 5'-(N-cyclopropyl)-carboxamidoadenosine; cerebral blood flow; nitric oxide; adenylate cyclase; guanylate cyclase;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Bredt, D. S., Glatt, C. E., Hwang, P. M., Fotuhl, M., Dawson, T. M. and Snyder, S. H. (1991). Nitric oxide synthetase protein and m-RNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron 7, 615-624   DOI   ScienceOn
2 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 AI-selective adenosine antagonist 8-cyclopentyl- l,3-diproxylxanthine to rat brain membranes. Naunyn-Schmiedebergs Arch. Pharmacol. 335, 59-63
3 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. Phannacol. Exp. Ther. 242, 905-910
4 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   DOI   ScienceOn
5 Dimagl, U., Lindauer, U. and Villringer, A. (1993). Role of nitric oxide in the coupling of cerebral blood flow to neuronal activation in rats. Neurosei. Lett. 149, 43-46   DOI   ScienceOn
6 Dirnagl, U., Niwa, K., Lindauer, U. and Villringer, A. (1994). Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide. Am. J. Physiol. 267, H296-H301
7 Fredholm, B. B., Abbrachio, M. P., Burnstock, 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
8 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
9 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. Circ. Physiol. 270, H317-H323
10 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   DOI
11 Ibayashi, S., Ngai, A. C., Meno, J. R. and Winn, H. R. (1991). Effects of topical adenosine analogs and forskolin on rat pial arterioles in vivo. J. Cereb. Blood. Flow. Metab. 11, 72-76   DOI
12 Janigro, D., Wender, R., Ransom, G., Tinklepaugh, D. L. and Winn, H. R. (1996). Adenosine-induced release of nitric oxide from cortical astrocytes. NeuroReport 7, 1640-1644   DOI   ScienceOn
13 Jiang, H., Colbran, J. L., Francis, S. H. and Corbin, J. D. (1992). Direct evidence for cross-activation of cGMPdependent protein kinase by cAMP in pig coronary arteries. J. BioI. Chem. 267, 1015-1019
14 Liang, B. T. and Haltiwanger B. (1995). Adenosine A$_2$receptors in cultured fetal chick heart cells. Cire. Res. 76, 243-251
15 Akgoren, N., Fabricius, M. and Lauritzen, M. (1994). Importance of nitric oxide for local increases of blood flow in rat cerebellar cortex during electrical stimulation. Proe. Natl. Aead. Sci. 91, 5903-5907   DOI   ScienceOn
16 Barraco, R. A., Campbell, W. R., Parizon, M., Shoener, E. P. and Shein, S. E. (1987). Cardiovascular effects of microinjections of adenosine analogs into the fourthventricle of rats. Brain Res. 424, 17-25   DOI   ScienceOn
17 Thomas, T. and Marshall, J. M. (1994). Interdependence of respiratory and cardiovascular changes induced by systemic hypoxia in the rat: the role of adenosine. J. Physiol. 480, 627-636
18 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   DOI
19 Vials, A. and Burnstock, G. (1993). A$_2$-purinoceptor-mediated relaxtion in the guinea-pig coronary vasculature: a role for nitric oxide. Br. J. Pharmacal. 109, 424-429
20 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   DOI
21 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   DOI
22 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   DOI   ScienceOn
23 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   DOI   ScienceOn
24 Gerber, U. and Giihwiler, 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
25 Goadsby, P. J., Kaube, H. and Hoskin, K. L. (1992). Nitric oxide synthesis couples cerebral blood flow and Metabolism. Brain Res. 595, 167-170   DOI   ScienceOn
26 Hong, K. W., Pyo, K. M., Lee, W. S., Yu, S. Sand Rhim, B. y. (1994). Pharmacological evidence that calcitonin-related peptide is implicated in cerebral autoregulation. Am. J. Heart. Circ. Physiol. 266, H11-H16
27 Phillis, J. W. (1989). Adenosine in the control of the cerebral circulation. Cerebrovasc. Brain Metab. Rev. 1, 26-54
28 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
29 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   DOI
30 Olah, M. E. and Stiles, G. L. (1996). Adenosine receptor subtypes: characterization and therapeutic regulation. Annu. Rev. Pharmacal. Toxicol. 35, 581-606
31 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
32 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   DOI
33 Zhou, H. L. and Torphy, T. J. (1991). Relationship between cyclic guanosine monophosphate accumulation and relaxation of canine trachealis induced by nitrovasodilators. J. Pharmacal. Exp. Ther. 258, 972-978