Ca2+ release triggered by NAADP in hepatocyte microsomes.
NAADP (nicotinic acid-adenine dinucleotide phosphate) is fast emerging as a new intracellular Ca2+-mobilizing messenger. NAADP induces Ca2+ release by a mechanism that is distinct from IP3 (inositol 1,4,5-trisphosphate)- and cADPR (cADP-ribose)-induced Ca2+ release. In the present study, we demonstrated that micromolar concentrations of NAADP trigger Ca2+ release from rat hepatocyte microsomes. Cross-desensitization to IP3 and cADPR by NAADP did not occur in liver microsomes. We report that non-activating concentrations of NAADP can fully inactivate the NAADP-sensitive Ca2+-release mechanism in hepatocyte microsomes. The ability of thapsigargin to block the NAADP-sensitive Ca2+ release is not observed in sea-urchin eggs or in intact mammalian cells. In contrast with the Ca2+ release induced by IP3 and cADPR, the Ca2+ release induced by NAADP was completely independent of the free extravesicular Ca2+ concentration and pH (in the range 6.4-7.8). The NAADP-elicited Ca2+ release cannot be blocked by the inhibitors of the IP3 receptors and the ryanodine receptor. On the other hand, verapamil and diltiazem do inhibit the NAADP- (but not IP3- or cADPR-) induced Ca2+ release.
Mándi
Miklós
M
Department of Medical Biochemistry, Semmelweis University, Puskin Street 9, P.O. Box 262, Budapest, H-1444, Hungary. mickeyka@freemail.hu
Tóth
Balázs
B
Timár
György
G
Bak
Judit
J
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000187:drug effects; D018942:Macrolides / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D018942:Macrolides; D011956:Receptors, Cell Surface; D009249:NADP; C024376:NAADP; D019284:Thapsigargin; C040929:bafilomycin A1; D002118:Calcium