Kawaguchi H, Sano H, Iizuka K, Okada H, Kudo T, Kageyama K, Muramoto S, Murakami T, Okamoto H, Mochizuki N
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Circ Res. 1993 May;72(5):966-72. doi: 10.1161/01.res.72.5.966.
The accumulation of inositol 1,4,5-trisphosphate (IP3) after hormonal stimulation has a physiological role, possibly by alteration of Ca2+ levels in cardiac myocyte. However, this accumulation has not been studied under pathophysiological conditions. In this report, we examine phosphatidylinositol metabolism during cellular response to norepinephrine in pressure-overloaded hypertrophic rat heart. After stimulation with norepinephrine, the accumulations of IP3 and diacylglyceride significantly increased in isolated myocytes from stroke-prone spontaneously hypertensive rat (SHRSP) heart, indicating phosphatidylinositol-specific phospholipase C activity increased in SHRSP heart cells. Protein kinase C activity was also enhanced in SHRSP, with a marked increase in particulate activity. We determined the intracellular calcium concentration and found it to be higher in SHRSP than in Wistar-Kyoto (WKY) rats at 30-40 weeks of age. Ca2+ influx was also elevated in SHRSP stimulated by norepinephrine. In SHRSP heart, cytosolic Ca2+ concentration may rise quickly in response to some stimuli, such as alpha 1-adrenergic stimulation, which is shown to be one of the pathways that increases cytosolic Ca2+ levels in hypertrophied rat heart. These data suggest that a part of the phosphatidylinositol-turnover pathway, such as the phosphatidylinositol 4,5-bisphosphate-IP3-Ca2+ pathway or the diacylglyceride-protein kinase C pathway, may play an important role in the development of hypertrophy in SHRSP heart.
激素刺激后肌醇1,4,5 -三磷酸（IP3）的积累具有生理作用，可能是通过改变心肌细胞中的Ca2+水平来实现的。然而，这种积累在病理生理条件下尚未得到研究。在本报告中，我们研究了压力超负荷肥厚大鼠心脏中细胞对去甲肾上腺素反应过程中的磷脂酰肌醇代谢。用去甲肾上腺素刺激后，易卒中型自发性高血压大鼠（SHRSP）心脏分离的心肌细胞中IP3和二酰甘油的积累显著增加，表明SHRSP心脏细胞中磷脂酰肌醇特异性磷脂酶C活性增加。SHRSP中的蛋白激酶C活性也增强，颗粒活性显著增加。我们测定了细胞内钙浓度，发现30 - 40周龄的SHRSP大鼠比Wistar - Kyoto（WKY）大鼠的细胞内钙浓度更高。去甲肾上腺素刺激的SHRSP中Ca2+内流也升高。在SHRSP心脏中，细胞溶质Ca2+浓度可能会对某些刺激（如α1 -肾上腺素能刺激）迅速升高，这被证明是肥厚大鼠心脏中增加细胞溶质Ca2+水平的途径之一。这些数据表明，磷脂酰肌醇代谢途径的一部分，如磷脂酰肌醇4,5 -二磷酸 - IP3 - Ca2+途径或二酰甘油 - 蛋白激酶C途径，可能在SHRSP心脏肥大的发展中起重要作用。
