Phosphoinositide metabolism and metabolism-contraction coupling in rabbit aorta
- Univ. of Pennsylvania, Philadelphia (USA)
The authors tested a hypothesis that metabolism-contraction coupling in vascular smooth muscle is controlled by the rate of delivery of energy to ATP-dependent reactions in the inositol phospholipid transduction system that generate second messengers exerting control on smooth muscle force. Rabbit aorta was contracted by norepinephrine (NOR) under conditions of normoxia and hypoxia, and changes in inositol phospholipid pool sizes and metabolic flux rates (J{sub F}) were determined. J{sub F} was determined by labeling free cytosolic myo-inositol by incubation of unstimulated muscle with myo-({sup 3}H)inositol and then measuring rates of incorporation of this isotope into inositol phospholipids and inositol phosphates when the muscle was activated by NOR. J{sub F} measured during maintenance of NOR-induced force was markedly inhibited during hypoxia to 40-50% of that determined during normoxia; rates of increases in inositol phosphate radioactivities were similarly depressed during NOR activation under hypoxia. The hypoxia-induced decrease in J{sub F} was associated with four- to fivefold increase in phosphatidylinositol 4-phosphate (PIP) total pool size, suggesting PIP kinase was inhibited and rate limiting. These data suggest that activation of inositol phospholipid metabolism, which generates inositol 1,4,5-trisphosphate (IP{sub 3}) and diacylglycerol, is blunted under conditions where aerobic energy production is inhibited. Data are consistent with rate-limiting effects of decreased ATP delivery, or decreased phosphate potential, on PIP kinase and reactions that control resynthesis of phosphatidylinositol.
- OSTI ID:
- 6227895
- Journal Information:
- American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 255:6; ISSN 0002-9513; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANOXIA
AORTA
ARTERIES
BLOOD VESSELS
BODY
CARBOHYDRATES
CARDIOVASCULAR SYSTEM
ESTERS
HYDROGEN COMPOUNDS
INOSITOLS
LIPIDS
MAMMALS
METABOLISM
MONOSACCHARIDES
MUSCLES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHOLIPIDS
PHYSIOLOGY
RABBITS
SACCHARIDES
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES