Changes in inositol 1,4,5-triphosphate binding in microsomal fractions from the rat liver during sepsis.
Inositol 1,4,5-triphosphate has been proposed as a second messenger for calcium mobilization. The addition of inositol 1,4,5-triphosphate at a low concentration has been shown to cause calcium release from intracellular microsomal stores in rat hepatocytes. The effects of sepsis on the inositol 1,4,5-triphosphate binding from microsomal fractions of rat liver were investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham operated. Three microsomal fractions (rough, intermediate, and smooth I) were isolated from the rat liver. The study of inositol 1,4,5-triphosphate receptor binding was performed with tritium-labeled inositol 1,4,5-triphosphate. Our results showed that the Bmax of inositol 1,4,5-triphosphate binding in early septic, late septic, and control groups was 14.9 +/- .9 fmol/mg, 9.8 +/- 1.0 fmol/mg, and 17.2 +/- 1.3 fmol/mg, respectively. The binding activity was unaffected during early sepsis but was significantly depressed by 40-50% (p < .05, vs. control) during late sepsis (18 h after CLP) in all three subfractions of endoplasmic reticulum. Because the inositol 1,4,5-triphosphate binding plays an important role in the regulation of intra-cellular calcium homeostasis in hepatocytes, an impairment of the calcium release due to depressed inositol 1,4,5-triphosphate binding in the endoplasmic reticulum may have a pathophysiological significance in contributing to altered hepatic metabolism during septic shock.
Hwang
T L
TL
Department of Surgery and Physiology, Chang Gung Medical College, Taiwan.
Liu
M S
MS
Yang
J
J
Lau
Y T
YT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems; D018805:Sepsis / Q000378:metabolism*; D013997:Time Factors
D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium