| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Research Abstract |
The primary event in the mechanism of action of many different hormones and neurotransmitters involves receptor-mediated stimulation of the breakdown of plasma membrane inositol phospholipids. This so-called phosphatidylinositol (PI) turnover pathway generates two second messengers, inositol- (1, 4,5) trisphosphate (IP_3) and sn 1, 2-diacyglycerol (DAG). DAG stimulates membrane-bound phospho-lipid-dependent, Ca^<2+>-dependent protein kinase C while IP_3, releases Ca^<2+> from endoplasmic reticulum stores. We consider that Plーturnover pathway has a quite important role in inducing cardiac myocyte hypertrophy. The purpose of this experiment is to study the properties of inositoltrisphostate kinase in hypertrophied rat heart.
In the present experiment, we demonstrated that inositol- (1, 4, 5) tris-phosphate (IP_3) kinase activity was increased in the stroke-prone spontaneously hypertensive rat (SHRSP) heart compared to the Wistar Kyoto rat (WKY). IP_3 kinase activity in the heart was highest in the cytosolic fraction in both SHRSP and WKY. Its activity progressively increased with age in SHRSP aged 5 to 20 weeks. The activity reached about three times the level of 5-week-old SHRSP in 40-weeks-old SHRSP. On the other hand, in WKY it was 1.3-fold at 40 weeks compared with 5-week-olds. We determined the effect of divalent cations on IP_3 kinase activity. Ca^<2+> stimulated its activity in a dose-dependent manner at 10^<-9> to 10^<-6>M. In SHRSP it was enhanced about 2.1-fold at 10^<-6>M of Ca^<2+>, but in WKY it was 1.5-fold at 10^<-6>M of Ca^<2+>. Mn^<2+> also stimulated IP_3 kinase activity in both groups of animals, while, Fe^<2+>, Zn^<2+>, and Cu^<2+> inhibited IP_3 kinase activity. In our experiment IP_3 kinase activity was increased in SHRSP and its activity was markedly affected by divalent cations. These data suggest the accumulations of IP_3 and IP_4 after hormonal stimulation have a physiologic role, possibly by alteration of Ca^<2+> levels in cardiac tissue.
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