The role of a purinergic P2z receptor in calcium-dependent cell killing of isolated rat hepatocytes by extracellular adenosine triphosphate
✍ Scribed by J P Zoetewij; B van de Water; H J de Bont; J F Nagelkerke
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 241 KB
- Volume
- 23
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
Extracellular adenosine triphosphate (ATP o ) (0.4 cells. 1,2 Changes in [Ca 2/ ] i have been implicated as a mmol/L), a P 2 -purinergic receptor agonist, induces cytolmajor factor in the cellular responses to ATP o . [2][3][4][5][6][7][8][9][10] Physysis in several cell types including isolated rat hepatoiological stimuli require ATP o concentrations in the micytes. In this study, we investigated the P 2 -receptor incromolar range. 2 Sometimes ATP o is locally present at volved in ATP o -induced, Ca 2/ -dependent cytotoxicity in much higher concentrations, e.g., in the immediate surhepatocytes. Pretreatment of hepatocytes with oxidized roundings of injured ATP-rich cells or after local spe-ATP, a P 2Z -receptor antagonist, or complexation of cific ATP secretion. 2,8,11,12 ATP 40 (the agonist for the P 2Z -receptor) with an excess Exposure to ATP causes cell death in hepatocytes, 13 of Mg 2/ , prevented ATP o -induced cell death. Both protecthis cytotoxic effect is associated with mitochondrial tive treatments also prevented the development of a sus-Ca 2/ accumulation, cellular inorganic phosphate (P i ) tained high intracellular Ca 2/ concentration as well as the subsequent accumulation of inorganic phosphate accumulation, and mitochondrial dysfunction. 13,14 Iso-(P i ). The P 2Z -receptor agonist 3-0-(4-benzoylbenzoyl)-lated rat hepatocytes express at least two types of P 2 -ATP (BzATP) was twofold more potent than ATP in elicpurinergic receptors, one of which belongs to the P 2yiting cytolysis, which was preceded by a sustained high receptor subclass. 2,15-17 So far, it is unknown which of intracellular Ca 2/ concentration; pretreatment with oxithe purinergic P 2 -receptor subtypes is involved in the dized ATP prevented both the increase in the intracellu-Ca 2/ -dependent cytolytic effects in hepatocytes. Morelar Ca 2/ concentration and cell death. Prevention of over, until recently, the physiological significance of ATP o -induced cell death, as well as the increases in the this cell killing was questionable. However, recently it intracellular Ca 2/ concentration and inorganic phos-