Narayan P, Valdivia H H, Mentzer R M, Lasley R D
Department of Surgery, University of Kentucky College of Medicine, Lexington 40536, USA.
J Mol Cell Cardiol. 1998 May;30(5):913-21. doi: 10.1006/jmcc.1998.0648.
It has been suggested that adenosine cardioprotection occurs via adenosine A1 receptor-mediated activation of protein kinase C (PKC). However, adenosine has well-known vasodilatory effects in the myocardium, whereas PKC is a vasoconstrictor. This study examined whether adenosine A1 receptor activation alters the effects of the PKC activator. 1,2-dioctanoyl-s,n-glycerol (DOG) in isolated perfused rat hearts (left-ventricular developed pressure) and rat ventricular myocytes ([Ca2+]i and cell shortening). Exposure to DOG decreased left-ventricular developed pressure by 30%, an effect that was completely reversible. Pretreatment of isolated hearts with either the PKC inhibitor chelerythrine or the adenosine A1 agonist 2-chloro-N6-cyclo-cyclo-isolated pentlyadenosine (CCPA) attenuated the negative inotropic effects of DOG. In the isolated myocytes, DOG decreased [Ca2+]i and cell shortening by 25 and 28%, respectively, effects that were attenuated by both chelerythrine and CCPA. The CCPA attenuation of the DOG-induced decrease in [Ca2+]i and cell shortening was blocked by pretreating the myocytes with the adenosine A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). These results indicate that in rat ventricular myocardium, adenosine A1 receptor activation attenuates the apparent PKC-dependent negative inotropic effects of DOG via preservation of [Ca2+]i levels.
有人提出，腺苷的心脏保护作用是通过腺苷A1受体介导的蛋白激酶C（PKC）激活来实现的。然而，腺苷在心肌中具有众所周知的血管舒张作用，而PKC是一种血管收缩剂。本研究探讨了腺苷A1受体激活是否会改变PKC激活剂1,2-二辛酰-s,n-甘油（DOG）的作用。在离体灌注大鼠心脏（左心室舒张末压）和大鼠心室肌细胞（[Ca2+]i和细胞缩短）中进行了研究。暴露于DOG使左心室舒张末压降低30%，这一作用完全可逆。用PKC抑制剂白屈菜红碱或腺苷A1激动剂2-氯-N6-环戊基腺苷（CCPA）预处理离体心脏，可减弱DOG的负性肌力作用。在离体心肌细胞中，DOG使[Ca2+]i和细胞缩短分别降低25%和28%，白屈菜红碱和CCPA均可减弱这一作用。用腺苷A1拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX）预处理心肌细胞可阻断CCPA对DOG诱导的[Ca2+]i降低和细胞缩短的减弱作用。这些结果表明，在大鼠心室心肌中，腺苷A1受体激活通过维持[Ca2+]i水平减弱了DOG明显的PKC依赖性负性肌力作用。
