Inositol trisphosphate and thapsigargin discriminate endoplasmic reticulum stores of calcium in rat brain.
ATP dependent Ca2+ accumulation into oxalate-loaded rat brain microsomes is potently inhibited by thapsigargin with an IC50 of 2 nM and maximal inhibition at 10 nM. Approximately 15% of the total A23187-releasable microsomal calcium store is insensitive to thapsigargin concentrations up to 100 microM. Inositol-1,4,5-trisphosphate (IP3) maximally inhibits 40% of the net Ca2+ accumulation by whole brain microsomes. Its effects are non-additive with thapsigargin suggesting that the IP3-sensitive Ca2+ pool is a subset of the thapsigargin sensitive Ca2+ pool. Marked regional differences occur in Ca2+ transport rates and sensitivity to both thapsigargin and IP3.
Verma
A
A
Johns Hopkins University School of Medicine, Department of Neuroscience, Baltimore, Maryland 21205.
Hirsch
D J
DJ
Hanley
M R
MR
Thastrup
O
O
Christensen
S B
SB
Snyder
S H
SH
D000818:Animals; D001921:Brain / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D002273:Carcinogens; D013729:Terpenes; D000001:Calcimycin; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D002118:Calcium