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.