N, N-dimethyl-D-erythro-sphingosine increases intracellular Ca2+ concentration via Na+-Ca2+-exchanger in HCT116 human colon cancer cells.
N,N-dimethyl-D-erythro-sphingosine (DMS), an N-methyl derivative of sphingosine, is an inhibitor of protein kinase C (PKC) and sphingosine kinase (SK). In previous reports, DMS-induced intracellular Ca2+ increase concentration ([Ca2+]i) was studied in T lymphocytes, monocytes, astrocytes and neuronal cells. In the present study, we studied DMS-induced increase of [Ca2+]i in HCT116 human colon cancer cells. We found that the DMS-induced increase of [Ca2+]i in colon cancer cells is composed of Ca2+ release from intracellular Ca2+ stores and subsequent Ca2+ influx. The Ca2+ release is not related to modulation of inositol 1,4,5-trisphosphate (IP3) receptor or ryanodine receptor. On the other hand, the Ca2+ influx is mediated largely through Ca2+ channels sensitive to verapamil, nifedipine, Ga3+, and La3+. Furthermore, we found that the response is inhibited by bepridil and Ni2+, specific inhibitors of Na+-Ca2+-exchanger, suggesting involvement of Na+-Ca2+ exchanger in the DMS-induced [Ca2+]i increase in colon cancer cells. This inhibition was also observed in U937 monocytes, but not in 1321N1 astrocytes.
Kim
Hyo-Lim
HL
Laboratory of Pharmacology, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Im
Dong-Soon
DS
D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D045325:HCT116 Cells; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000187:drug effects; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D004533:Egtazic Acid; D019284:Thapsigargin; C061800:N,N-dimethylsphingosine; D013110:Sphingosine; D002118:Calcium