Schwartz D D, Williams J L, Malik K U
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
Am J Physiol. 1993 Sep;265(3 Pt 1):E439-45. doi: 10.1152/ajpendo.1993.265.3.E439.
The present study was performed to investigate the contribution of adenosine 3',5'-cyclic monophosphate (cAMP) and calcium to isoproterenol-stimulated lipolysis in the isolated rabbit heart perfused with Krebs-Henseleit buffer according to the method of Langendorff. Isoproterenol (0.05-1.5 nmol) increased glycerol output, left ventricular dP/dtmax, and heart rate but decreased coronary perfusion pressure. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (50 microM) failed to alter the basal or isoproterenol-induced increase in glycerol output, whereas cilostamide (5 microM) enhanced basal and inhibited isoproterenol-stimulated glycerol output. Inhibition of adenylyl cyclase with (phenylisopropyl)adenosine reduced isoproterenol-stimulated mechanical parameters but had no effect on basal or isoproterenol-stimulated glycerol output, whereas the cAMP analogue 8-(4-chlorophenylthio)-cAMP did not increase glycerol output but produced changes in mechanical parameters similar to isoproterenol. Decreasing perfusion fluid calcium concentration from 1.2 to 0.5 mM or infusion of the calcium channel antagonist diltiazem (23 microM) abolished the increase in glycerol output in response to isoproterenol. Activation of adenylyl cyclase with forskolin increased glycerol output, but the increase was abolished by reducing perfusion fluid calcium concentration or by diltiazem. These data suggest that, in the rabbit heart, isoproterenol-stimulated lipolysis appears to be mediated predominantly by calcium as a secondary metabolic response provided by the increase in mechanical activity.
本研究旨在根据Langendorff方法，研究3',5'-环磷酸腺苷（cAMP）和钙对在Krebs-Henseleit缓冲液中灌注的离体兔心脏中异丙肾上腺素刺激的脂解作用的贡献。异丙肾上腺素（0.05 - 1.5 nmol）增加了甘油输出、左心室dp/dtmax和心率，但降低了冠状动脉灌注压。磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（50 μM）未能改变基础或异丙肾上腺素诱导的甘油输出增加，而西洛他唑（5 μM）增强了基础甘油输出并抑制了异丙肾上腺素刺激的甘油输出。用（苯异丙基）腺苷抑制腺苷酸环化酶降低了异丙肾上腺素刺激的机械参数，但对基础或异丙肾上腺素刺激的甘油输出没有影响，而cAMP类似物8-（4-氯苯硫基）-cAMP没有增加甘油输出，但产生了与异丙肾上腺素类似的机械参数变化。将灌注液钙浓度从1.2 mM降至0.5 mM或注入钙通道拮抗剂地尔硫䓬（23 μM）消除了对异丙肾上腺素的甘油输出增加。用福斯可林激活腺苷酸环化酶增加了甘油输出，但通过降低灌注液钙浓度或地尔硫䓬可消除这种增加。这些数据表明，在兔心脏中，异丙肾上腺素刺激的脂解作用似乎主要由钙介导，作为机械活动增加所提供的次级代谢反应。
