Effect of cytoplasmic Ca2+ on (1,4,5)IP3 formation in vasopressin-activated hepatocytes.
The role of cytoplasmic calcium as a regulator of phospholipase C in vasopressin-activated hepatocytes was examined. According to models in which calcium spiking arises because of a positive feedback by calcium on phospholipase C, Ca2+ is seen as a positive modulator of phospholipase C under conditions of submaximal receptor activation. However, in hepatocytes whose precursor lipids had been labeled by incubation in [3H]-inositol, no increase in [3H]-(1,4,5)IP3 was detected in response to thapsigargin, in either unstimulated cells, or in cells stimulated with 1 nM vasopressin. Addition of a maximal concentration of vasopressin (1 microM) caused a rapid and substantial increase in [3H]-(1,4,5)IP3. These results indicate that changes in cytoplasmic calcium do not influence phospholipase C activity in hepatocytes, even under conditions of submaximal agonist activation. These findings also support models that provide for calcium spiking at constant levels of (1,4,5)IP3 at least in the case of the rat hepatocyte.
Bird
G S
GS
Calcium Regulation Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Obie
J F
JF
Putney
J W
JW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012076:Renal Agents / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014316:Tritium; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D012076:Renal Agents; D014662:Vasoconstrictor Agents; D014316:Tritium; D014667:Vasopressins; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium