Differential Modulation of Exogenous and Endogenous Adenosine- induced Coronary Vasodilation by Dipyridamole

• 영문명: Differential Modulation of Exogenous and Endogenous Adenosine- induced Coronary Vasodilation by Dipyridamole
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Young-Hoon Kim Chan-Hyung Kim Myung-Suk Kim
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제5권 제5호, 423~431쪽, 전체 9쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2001.01.01

영문 초록

Some recent investigations revealed that vasodilatory action of adenosine is mainly not mediated by surface A2 receptor and suggested the existence of an intracellular action site. In the present study, we tried to differentiate intracellular from extracellular site of adenosine action in the regulation of coronary flow. In perfused rabbit hearts, concentration-response curve of coronary flow to exogenous adenosine was constructed in the presence or absence of dipyridamole, an inhibitor of transmembrane purine transport. Inhibition of cellular adenosine uptake by dipyridamole suppressed the increase of flow rate while enhancing the decrease in heart rate induced by exogenous adenosine. In another series of experiments, perfused rabbit hearts were subjected to energy deprivation in order to increase the production of endogenous adenosine. Energy deprivation along with dipyridamole administration resulted in higher coronary flow rate. Lower perfusate adenosine concentration was observed along with higher tissue adenosine content in this group. These results implied that coronary flow rate is determined not by interstitial adenosine concentration but by intracellular activity of adenosine. To confirm the effects of dypiridamole in vivo, direct measurement of interstitial adenosine concentration by mycrodialysis along with the assay of intracellular adenosine content was performed after intranenous dipyridamole administration. After dipyridamole infusion, intracellular adenosine content was markedly increased while interstitial adenosine concentration was not altered. In another series of experiments, the right shift of concentration-response curve of adenosine-induced vasodilation by 8-phenyltheophilline, a representative adenosine receptor antagonist, was mostly abolished by prior administration of prazosin, indicating that the influence of 8-PT on the adenosine action is not attributed to the inhibition of A2 receptor but related to the suppression of α-adrenoceptor activation. From these results, we concluded that adenosine acts intracellularly to regulate the coronary blood flow.

키워드

Adenosine Dipyridamole Vasodilation A2 receptor 8-phenyltheophylline