Heparin inhibits inositol trisphosphate-induced calcium release from permeabilized rat liver cells.
Neoplastic rat liver epithelial (261B) cells made permeable by electroporation released 0.2-0.3 microM Ca2+ from intracellular stores in response to 0.5 microM Ins(1,4,5)P3 stimulation. This Ca2+ release response was found to be inhibited by heparin in a dose-dependent manner (Ki of 15 micrograms/ml). Two other glycosaminoglycans, chondroitin sulfate and hyaluronic acid, showed no inhibitory effect at doses as high as 0.2 mg/ml. Passive Ca2+ release, and sequestration of Ca2+ into intracellular storage sites by the action of Ca2+-ATPase were unaffected by heparin treatment. We conclude that the inhibitory action of heparin treatment on Ca2+ mobilization in permeabilized 261B cells is mediated through its interaction at the Ins(1,4,5)P3 receptor binding site.
Hill
T D
TD
Basic Science Unit, Cancer Research Center of Hawaii, Honolulu 96813.
Berggren
P O
PO
Boynton
A L
AL
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D013403:Sugar Phosphates / Q000037:antagonists & inhibitors*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D000252:Calcium-Transporting ATPases; D002118:Calcium