G-PROTEIN-COUPLED RECEPTORS IN HL-60 HUMAN LEUKEMIA-CELLS

Citation
Jf. Klinker et al., G-PROTEIN-COUPLED RECEPTORS IN HL-60 HUMAN LEUKEMIA-CELLS, General pharmacology, 27(1), 1996, pp. 33-54
Citations number
236
Categorie Soggetti
Pharmacology & Pharmacy
Journal title
ISSN journal
03063623
Volume
27
Issue
1
Year of publication
1996
Pages
33 - 54
Database
ISI
SICI code
0306-3623(1996)27:1<33:GRIHHL>2.0.ZU;2-Q
Abstract
1. HL-60 human leukemia cells are a widely employed model system for t he analysis of signal transduction processes mediated via regulatory h eterotrimeric guanine nucleotide binding proteins (G-proteins). HL-60 promyelocytes are pluripotent and can be differentiated into neutrophi lic or monocytic cells. 2. HL-60 cells express formyl peptide, complem ent C5a-, leukotriene B-4 (LTB(4)) and platelet-activating factor rece ptors, receptors for purine and pyrimidine nucleotides, histamine H-1- and H-2-receptors, beta(2)-adrenoceptors and prostaglandin receptors. 3. The major G-proteins in HL-60 cells are pertussis toxin (PTX) sens itive G(i)-proteins (G(i2) > G(i3)), G(s)-proteins and G-proteins of t he G(q)-family (e.g., G(16)) are expressed, too. 4. G-protein regulate d effector systems in HL-60 cells are adenylyl cyclase and phospholipa se C-beta(2) (PLC-beta(2)) and, possibly, phospholipase D(PLD), nonsel ective cation (NSC) channels and NADPH oxidase. 5. The expression of s ignal transduction pathways in HL-60 cells strongly depends on the dif ferentiation state of cells. 6. Formyl peptides, via G(i)-proteins, me diate activation of PLC, PLD, NSC channels, NADPH oxidase and azurophi lic granule release and are referred to as full secretagogues. In dibu tyryl cAMP (Bt(2)cAMP)-differentiated HL-60 cells, C5a and LTB(4) are partial and incomplete secretagogues, respectively. There are substant ial differences in the G(i)-protein activations induced by formyl pept ides, C5a and LTB(4). 7. In HL-60 promyelocytes, purine and pyrimidine nucleotides mediate activation of PLC and NSC channels largely via PT X insensitive G proteins and induce functional differentiation. In Bt( 2)cAMP-differentiated HL-60 cells, they additionally activate PLD, NAD PH oxidase and granule release via PTX sensitive and insensitive pathw ays. ATP and UTP are partial secretagogues, Multiple types of receptor s (i.e., P-2Y- and P-2U-receptors and pyrimidinocyeptors) may mediate the effects of nucleotides in HL-60 cells. 8. Bt(2)cAMP and 1 alpha,25 -dihydroxycholecalciferol-differentiated HL-60 cells express H-1-recep tors coupled to G(i)-proteins and PTX insensitive G-proteins. In the f ormer cells, histamine mediates activation of PLC and NSC channels, an d in the latter, activation of NSC channels. Histamine is an incomplet e secretagogue in these cells. 9. HL-60 promyelocytes express H-2-rece ptors coupled to adenylyl cyclase, PLC, and NSC channels. There are su bstantial differences in the agonist/antagonist profiles of H-2-recept or mediated cAMP formation and rises in cytosolic Ca2+ concentration, indicative of the involvement of different Hz receptor subtypes. H-2-r eceptors mediate functional differentiation of HL-60 cells. 10. Certai n cationic amphiphilic histamine receptor ligands (i.e., 2-substituted histamines, lipophilic guanidines, and a histamine trifluoromethyl-to luidide derivative) show stimulatory effects in HL-60 cells that are a ttributable to receptor independent activation of G(i)-proteins.