Predominantly via H2 Receptors with an Unique Agonist/ Antagonist Profile and Induces Functional Differentiation

Histamine H1 receptors mediate activation of phospholipase C, with subsequent increases in cytosolic Ca2 concentration ([Ca21), and H2 receptors mediate accumulation of cAMP. HL-60 promyelocytes possess H2 receptors, but it is not known whether these cells also possess H1 receptors. We studied the effects of histamine on [Ca2] and the functional importance of histamine receptors in HL-60 promyelocytes. In these cells, histamine and dimaprit increased [Ca2] with EC50 values of 15 tM and 30 ffM, respectively. Diphenhydramine inhibited the effect of histamine (1 00 M) on [Ca21 up to 40%, with an IC50 of 100 nM. Famotidine and cimetidine diminished the effect of histamine (100 ffM) up to 75#{176}Io,with IC50 values of 85 n and 300 n, respectively. Diphenhydramine plus famotidine abolished hista-mine-induced rises in [Ca2]. Impromidine, with an lC of 100 nM, abolished the effect of histamine (100 M) on [Ca2],. Di