KAWAHARA Yasuhiro Kobe University School of Medicine, Assistant Professor, 医学部, 助手 (80169755)
AKITA Hozuka Kobe University School of Medicine, Assistant Professor, 医学部, 助手 (60175792)
ISHIKAWA Yuichi Kobe University School of Medicine, Assistant Professor, 医学部, 講師 (90159707)
YOKOYAMA Mitsuhiro Kobe University School of Medicine, Associate Professor, 医学部, 助教授 (40135794)
山田 充彦 神戸大学, 医学部附属病院, 医員
|Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1989: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1988: ¥4,900,000 (Direct Cost: ¥4,900,000)
Cardiovascular system is regulated by various substances including hormones, autacoids, and neurotransriitters. Regulatory abnormalities induced by these substances can contribute to major cardiovascular pathological state like cardiac hypertrophy, cardiac failure, arteriosclerosis, and vascular spasm. Therefore, it is of crucial importance to clarify the molecular and cellular mechanisms of their actions. In the present project, we have attempted to elucidate a role of phosphoinositides(PI) hydrolysis in cardiac hypertrophy and contraction in cultured fetal ventricular myocytes.
(I) PI hydrolysis: It has previously been shown that PI hydrolysis plays important roles in the process of cardiac hypertrophy and contraction. We examined the effects of various substances on PI hydrolysis. Epinephrine and acetylcholine stimulated PI hydrolysis as reported previously. We found that fetal bovine serum(FCS), ATP, histamine, and serotonin also stimulated PI hydrolysis.
(II) Cardiac hypertrophy: We next examined effects of these substances on cardiac hypertrophy in the cultured myocytes. Myocyte growth is controlled by both pratein synthesis and degradation. We assessed protein degradation by measuring radioactivity of [^3H]phenylalanine released from prelabelled myocytes. FSC, serotonin, ATP, and phenylephrin inhibited protein degradation. Isoproterenol, ahich stimulate cyclic AMP(cAMP) accumulation, also ingibited protein degradation. Thus, it becomes evident that cardiac myocyte hypertrophy is induced by the two intracellular messenger systems; PI hydrolysis and cAMP.
(III) Cardiac contraction: It is established that cardiac contraction is under control of cAMP system. We found that FCS, serotonin, and phenylephrin, all of which stimulate PI hydrolysis, stimulated spontaneous beating of the cultured myocytes, as monitored by an optical edge-tracking method using a TV camera. Among them, serotonin is known to have positive inotropic and