Histamine H(1) receptor activation inhibits the proliferation of human prostatic adenocarcinoma DU-145 cells.

摘要

BACKGROUND: Histamine stimulates cell proliferation in some tumor cell lines through the activation of H(1) receptors coupled to phosphoinositide hydrolysis. We therefore set out to study the presence of H(1) 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 [(1)H]-inositol phosphate ([(1)H]-IPs) accumulation and changes in the intracellular concentration of free Ca(2+) ([Ca(2+)](i)). Proliferation was assessed by cell counting and by [(1)H]-thymidine incorporation. RESULTS: DU-145 cells express H(1) receptors (110+/-14 fmol/mg of protein) whose stimulation results in [(1)H]-IPs accumulation (602+/-23% of basal, EC(50) 2.2+/-0.4 microM) and calcium mobilization (resting level 96+/-5 nM, Delta[Ca(2+)](i) 517+/-32 nM, EC(50) 6.2+/-0.1 microM). Incubation with histamine (100 microM, 24 hr) resulted in a decrease in both cell number and [(1)H]-thymidine incorporation, blocked by the H(1) antagonist mepyramine (1 microM). CONCLUSIONS: Histamine inhibits the proliferation of DU-145 cells through the activation of H(1) receptors coupled to phosphoinositide hydrolysis. Copyright 2001 Wiley-Liss, Inc.