The development of new method of IP4 detection and the study of its intracellular distribution.

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Objective : Free cytosolic calcium plays an important role in the development of cell proliferation. Inositol 1,4,5-trisphosphate (IP3) is a second messenger releasing intracellular Ca^<2+> into the cytosol from sarcoplasmic reticulum (SR). We determined Ca^<2+> release from SR stimulated by IP3 in hypertrophied rat heart to investigate the relationship between cardiac hypertrophy and Ca^<2+>Design and Methods : Experiments were carried out on 10-30-week-old male spontaneously hypertensive rat (SHR) and age-matched normotensive Wistar-kyoto rat (WKY). Rat heart was homogenized and centrifuged at 105,000xg for 90 min. The resultant pellets were used as SR fraction. SR fractions were also obtained from SHR treated with alpha 1-blockade, bunazisin-HC1 (10 mg/Kg body weight/day) or beta-blockade, atenolol (20 mg/Kg body weight/day)Results : Ca^<2+> release stimulated by IP3 was detected at 1 M of IP3. The release was dose dependently increased by 5 M or IP3. The release was higher in 10-30 weeks old SHR compared with agematched WKY.Left ventricular weight was markedly decreased in SHR treated with alpha- or beta-blockade. Ca^<2+> release stimulated with IP3 was also suppressed in these SHR treated with antihypertensive drugs, significantly. Now we have been trying to purify IP4 binding protein.Conclusion : These results may suggest that IP3 and Ca^<2+> have an important role in cardiac hypertrophy in SHR.