Neuropeptide Y mobilizes intracellular Ca2+ and increases inositol phosphate production in human erythroleukemia cells.
The intracellular concentration of free Ca2+ was monitored by measuring the fluorescence of fura-2 loaded Human Erythroleukemia Cells. Neuropeptide Y (NPY) increased intracellular Ca2+ in a dose-dependent manner and the 50% effective concentration was 2 nM. Chelation of extracellular Ca2+ by EGTA did not reduce the NPY-mediated increase in cytoplasmic Ca2+, indicating that the increase in fluorescence was due to the release of intracellular Ca2+. A second dose of NPY, after intracellular Ca2+ had returned to basal levels, failed to elicit a response, indicating that the NPY receptor had undergone desensitization. In similar experiments, NPY increased the formation of inositol phosphates, suggesting that the mobilization of Ca2+ from intracellular stores in HEL cells was secondary to the generation of inositol phosphates and stimulation of phospholipase C.
Daniels
A J
AJ
Medicinal Biochemistry Division, Wellcome Research Laboratories, Research Triangle Park, N.C. 27709.
Lazarowski
E R
ER
Matthews
J E
JE
Lapetina
E G
EG
D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D001572:Benzofurans; D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D009478:Neuropeptide Y; D004533:Egtazic Acid; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2