Histamine H1 receptor activation inhibits the proliferation of human prostatic adenocarcinoma DU-145 cells

Background Histamine stimulates cell proliferation in some tumor cell lines through the activation of H1 receptors coupled to phosphoinositide hydrolysis. We therefore set out to study the presence of H1 receptors in the prostate cancer cell line DU‐145 and the effect of their stimulation on cell growth. Methods The presence of histamine receptors was studied by radioligand binding. Phosphoinositide hydrolysis was assessed by measuring [1H]‐inositol phosphate ([1H]‐IPs) accumulation and changes in the intracellular concentration of free Ca2+ ([Ca2+]i). Proliferation was assessed by cell counting and by [1H]‐thymidine incorporation. Results DU‐145 cells express H1 receptors (110±14 fmol/mg of protein) whose stimulation results in [1H]‐IPs accumulation (602±23% of basal, EC50 2.2±0.4 μM) and calcium mobilization (resting level 96±5 nM, Δ[Ca2+]i 517±32 nM, EC50 6.2±0.1 μM). Incubation with histamine (100 μM, 24 hr) resulted in a decrease in both cell number and [1H]‐thymidine incorporation, blocked by the H1 antagonist mepyramine (1 μM). Conclusions Histamine inhibits the proliferation of DU‐145 cells through the activation of H1 receptors coupled to phosphoinositide hydrolysis. Prostate 48:179–187, 2001. © 2001 Wiley‐Liss, Inc.