Kovacic-Milivojevic B, Schultz H D, Gardner D G
Metabolic Research Unit, University of California, San Francisco 94143.
Can J Physiol Pharmacol. 1991 Oct;69(10):1493-9. doi: 10.1139/y91-224.
Prostaglandins F2 alpha and E2 increase release of immunoreactive (irANP) in primary cultures of rat atrial cardiocytes. This effect is independent of cell density in the cultures and does not appear to operate through a cAMP-dependent mechanism. Studies that probed the PGF2 alpha effect with a number of different pharmacological antagonists suggest that it is tied to a calmodulin-dependent step. This latter effect does not appear to be related to increased calcium entry through voltage-gated channels in the plasma membrane nor to mobilization of ryanodine-sensitive intracellular calcium pools. Inhibitors of the lipoxygenase pathway, a second avenue of arachidonate metabolism, resulted in a decrease in irANP release from cultured atrial or ventricular cardiocytes. Leukotriene C4, a lipoxygenase product, had a modest effect to promote irANP release over a 24-h period. However, pretreatment of anesthetized rats with nordihydroguarietic acid, a lipoxygenase inhibitor, had no effect on stretch-dependent release of irANP from the heart in vivo. These findings suggest that the prostaglandins represent the more important group of arachidonate metabolites in regulating irANP release physiologically.
前列腺素F2α和E2可增加大鼠心房心肌细胞原代培养物中免疫反应性心房钠尿肽（irANP）的释放。这种作用与培养物中的细胞密度无关，且似乎不是通过环磷酸腺苷（cAMP）依赖性机制发挥作用。用多种不同的药理学拮抗剂探究前列腺素F2α作用的研究表明，它与钙调蛋白依赖性步骤有关。后一种作用似乎与通过质膜电压门控通道增加钙内流无关，也与雷诺丁敏感的细胞内钙库的动员无关。脂氧合酶途径是花生四烯酸代谢的另一条途径，其抑制剂可导致培养的心房或心室心肌细胞中irANP释放减少。脂氧合酶产物白三烯C4在24小时内对促进irANP释放有适度作用。然而，用脂氧合酶抑制剂去甲二氢愈创木酸预处理麻醉大鼠，对体内心脏中irANP的牵张依赖性释放没有影响。这些发现表明，在生理调节irANP释放方面，前列腺素是更重要的花生四烯酸代谢产物组。
