Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Effects of Adenylate Cyclase, Guanylate Cyclase and KATP Channel Blockade on the Cerebral Blood Flow Response Induced by Adenosine A2B Receptor Agonist in the Rats

  • Youn, Doo-Sang (Department of Pharmacology, College of Medicine, Hanyang University) ;
  • Shin, In-Chul (Department of Pharmacology, College of Medicine, Hanyang University)
  • Published : 2005.03.01
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Abstract

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, guanylate cyclase and potassium channel. In pentobarbital-anesthetized, pancuronium-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood flow from cerebral cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine A$_{2B}$ receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA; 4 umol/I) increased cerebral blood flow. This effect of NECA (4 umol/I) was not blocked by pretreatment with adenylate cyclase inhibitor, MDL-12,330 (20 umol/I). But effect of NECA (4 umol/I) was blocked by pretreatment with guanylate cyclase inhibitor, LY-83,583 (10 umol/I) and pretreatment with ATP-sensitive potassium channel inhibitor, glipizide (5 umol/I). 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 and ATP-sensitive potassium channel in the cerebral cortex of the rats.

Keywords

References

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