G-protein-coupled receptors in HL-60 human leukemia cells.

摘要: Abstract 1. HL-60 human leukemia cells are a widely employed model system for the analysis of signal transduction processes mediated via regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins). promyelocytes pluripotent and can be differentiated into neutrophilic or monocytic cells. 2. express formyl peptide-, complement C5a-, leukotriene B4 (LTB4)- platelet-activating factor receptors, receptors purine pyrimidine nucleotides, histamine H1- H2-receptors, β2-adrenoceptors prostaglandin receptors. 3. The major G-proteins in pertussis toxin (PTX)-sensitive Gi-proteins (Gi2 > Gi3). Gs-proteins Gq-family (e.g., G16) expressed, too. 4. G-protein-regulated effector systems adenylyl cyclase phospholipase C-β2 (PLC-β2) and, possibly, D (PLD), nonselective cation (NSC) channels NADPH oxidase. 5. expression pathways strongly depends on differentiation state 6. Formyl peptides, Gi-proteins, mediate activation PLC, PLD, NSC channels, oxidase azurophilic granule release referred to as full secretagogues. In dibutyryl cAMP (Bt2cAMP)-differentiated cells, C5a LTB4 partial incomplete secretagogues, respectively. There substantial differences Gi-protein activations induced by LTB4. 7. promyelocytes, nucleotides PLC largely PTX-insensitive induce functional differentiation. Bt2cAMP-differentiated they additionally activate PTX-sensitive -insensitive pathways. ATP UTP Multiple types (i.e., P2Y- P2U-receptors pyrimidinocyeptors) may effects 8. Bt2cAMP- 1α,25-dihydroxycholecalciferol-differentiated Hl-receptors coupled G-proteins. former mediates latter, channels. Histamine is an secretagogue these 9. H2-receptors cyclase, agonist/antagonist profiles H2-receptor-mediated formation rises cytosolic Ca2+ concentration, indicative involvement different H2-receptor subtypes. 10. Certain cationic-amphiphilic receptor ligands 2-substituted histamines, lipophilic guanidines, trifluoromethyl-toluidide derivative) show stimulatory that attributable receptor-independent Gi-proteins.