Histamine increases cytosolic Ca2+ in HL-60 promyelocytes predominantly via H2 receptors with an unique agonist/antagonist profile and induces functional differentiation
Seifert, R.; Höer, A.; Schwaner, I.; Buschauer, A.
Molecular Pharmacology 42(2): 235-241
1992
ISSN/ISBN: 0026-895X PMID: 1381044 Document Number: 396138
Histamine H-1 receptors mediate activation of phospholipase C, with subsequent increases in cytosolic Ca-2+ concentration ((Ca-2+)-i), and H-2 receptors mediate accumulation of cAMP. HL-60 promyelocytes possess H-2 receptors, but it is not known whether these cells also possess H-1 receptors. We studied the effects of histamine on (Ca-2+)-i and the functional importance of histamine receptors in HL-60 promyelocytes. In these cells, histamine and dimaprit increased (Ca-2+)-i with EC-50 values of 15 mu-M and 30 mu-M, respectively. Diphenhydramine inhibited the effect of histamine (100 mu-M) on (Ca-2+)-i, up to 40%, with an IC-50 of 100 nm. Famotidine and cimetidine diminished the effect of histamine (100 mu-M) up to 75%, with IC-50 values of 85 nm and 300 nM, respectively. Diphenhydramine plus famotidine abolished histamine-induced rises in (Ca-2+)-i. Impromidine, with an IC-50 of 100 nm, abolished the effect of histamine (100 mu-M) on (Ca-2+)-i. Diphenhydramine, famotidine, cimetidine, and impromidine showed marked noncompetitive antagonism with histamine. Histamine- induced increases in (Ca-2+)-i were largely due to influx of Ca-2+ from the extracellular space. Ca-2+ influx was inhibited by 1-(-beta(3-(4-methoxyphenyl)propoxyl)-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365). Histamine activated phospholipase C. Histamine induced expression of formyl peptide receptors, which effect was abolished by famotidine. In U-937 promonocytes and in the human erythroleukemia cell lines HEL and K-562, histamine did not induce rises in (Ca-2+)-i. Our data suggest the following. (I) In HL-60 promyelocytes, histamine increases (Ca-2+)-i predominantly via H-2 receptors and to a lesser extent via H-1 receptors. (ii) The agonist/antagonist profile of the H-2 receptor-mediated increases in (Ca-2+)-i differs markedly from that for cAMP accumulation, suggesting the involvement of different H-2 receptor subtypes. (iii) In HL-60 promyelocytes, histamine activates nonselective cation channels and induces functional differentiation via H-2 receptors.