Inositol phosphate release and metabolism in rat left atria.
The phosphatidylinositol (PtdIns) turnover pathway in intact heart tissue differs from that in most cell types in that products of the inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] kinase pathway are not detected in 3H-labeling studies. In contrast, Ins(1,4,5)P3 kinase products are detected in isolated neonatal cardiomyocytes. To understand the basis for the observed properties of the cardiac pathway, a detailed study of inositol phosphate (InsP) release has been undertaken by using isolated adult rat left atria. Addition of norepinephrine to 3H-labeled atria caused a slow increase in 3H-labeled Ins(1,4,5)P3 and a more rapid increase in 3H-labeled Ins(1,4)P2, its immediate dephosphorylation product. The mass of Ins(1,4,5)P3 was high in unstimulated atria (13.5 +/- 1.1 pmol/mg tissue, mean +/- SEM, n = 4) and did not change with stimulation. Measurements of the specific activities of Ins(1,4,5)P3 and PtdIns(4,5)P2 provided an estimate of the turnover rate of Ins(1,4,5)P3 that was 20- to 40-fold lower than the rate of accumulation of 3H label in InsP1 and InsP2. In agreement with this, specific activities of InsP1 and InsP2 were higher than the specific activity of InsP3 in both control and stimulated atria. Neomycin (5 mmol/L) did not inhibit the accumulation of 3H-labeled InsP1 and InsP2 in left atria, even though it reduced the accumulation of 3H label in Ins(1,4,5)P3, providing evidence that InsP1 and InsP2 do not derive primarily from Ins(1,4,5)P3. Stimulation with norepinephrine for 20 minutes resulted in a parallel decrease in 3H-labeled Ins(1,4,5)P3 and in Ins(1,4,5)P3 mass, demonstrating that atria do not contain two different pools of Ins(1,4,5)P3.(ABSTRACT TRUNCATED AT 250 WORDS)
Cellular Biochemistry Laboratory, Baker Medical Research Institute, Prahran, Australia.
E A
EA
Woodcock
M B
MB
Suss
K E
KE
Anderson
D000818:Animals; D000831:Animals, Newborn; D006325:Heart Atria; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007295:Inositol Phosphates; D015544:Inositol 1,4,5-Trisphosphate