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Histamine H 1 receptor activation inhibits the proliferation of human prostatic adenocarcinoma DU‐145 cells
Author(s) -
Valencia Sandra,
HernándezAngeles Adriana,
SoriaJasso LuisEnrique,
AriasMontaño JoséAntonio
Publication year - 2001
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.1096
Subject(s) - histamine , receptor , histamine receptor , endocrinology , cell growth , medicine , stimulation , biology , inositol phosphate , intracellular , chemistry , inositol , microbiology and biotechnology , biochemistry , antagonist
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 μM) and calcium mobilization (resting level 96±5 nM, Δ[Ca 2+ ] i 517±32 nM, EC 50 6.2±0.1 μM). Incubation with histamine (100 μM, 24 hr) resulted in a decrease in both cell number and [ 1 H]‐thymidine incorporation, blocked by the H 1 antagonist mepyramine (1 μM). Conclusions Histamine inhibits the proliferation of DU‐145 cells through the activation of H 1 receptors coupled to phosphoinositide hydrolysis. Prostate 48:179–187, 2001. © 2001 Wiley‐Liss, Inc.