Histamine augments b 2 -adrenoceptor-induced cyclic AMP accumulation in human prostate cancer cells DU-145 independently of known histamine receptors Judith Ramos-Jime ´nez a,b , Luis-Enrique Soria-Jasso c , Aurelio Lo ´ pez-Colombo d , Jorge-Alberto Reyes-Esparza e , Javier Camacho b , Jose ´ -Antonio Arias-Montan ˜o a, * a Departamento de Fisiologı ´a, Biofı´sica y Neurociencias, Cinvestav, Me ´xico, D.F., Mexico b Seccio ´ n Externa de Farmacologı ´a, Cinvestav, Me ´xico, D.F., Mexico c Escuela Superior de Medicina, IPN, Me ´xico, D.F., Mexico d CMN Manuel Avila Camacho, IMSS, Puebla, Pue., Mexico e Facultad de Farmacia, UAEM, Cuernavaca, Mor., Mexico biochemical pharmacology 73 (2007) 814–823 article info Article history: Received 17 October 2006 Accepted 27 November 2006 Keywords: DU-145 cells Adrenoceptors Histamine cAMP Adrenaline Noradrenaline abstract Androgen-independent prostate cancer cells DU-145 express a number of G protein-coupled receptors, including histamine H 1 receptors. There is evidence for the presence of b- adrenoceptors in the human prostate, and in this work we set out to characterise the expression of b-adrenoceptors by DU-145 cells, their linking to cyclic AMP (cAMP) formation and the possible modulation by histamine H 1 receptors of b-adrenoceptor function. Satura- tion [ 3 H]-dihydroalprenolol binding indicated that DU-145 cells express moderate levels of b-adrenoceptors (22.7  2.5 fmol/mg protein), which belong to the b 2 -subtype as assessed by inhibition by the antagonists ICI-118,551 and CGP-20712A. Inhibition of [ 3 H]-dihydroalpre- nolol binding by agonists (noradrenaline, adrenaline and isoproterenol) showed the pre- sence of both high-(53–59%) and low-affinity binding sites. b-Adrenoceptor stimulation with isoproterenol resulted in robust [ 3 H]-cAMP accumulation (10–30-fold of basal, EC 50 142 nM; pEC 50 6.85  0.05). While not having effect of its own on basal [ 3 H]-cAMP accumulation, histamine significantly augmented the b 2 -adrenoceptor-induced response (overall effect 152  6% of isoproterenol alone) with EC 50 1.35 mM (pEC 50 5.87  0.06). This effect was independent of extracellular Ca 2+ , insensitive to antagonists/agonists at H 1 ,H 2 or H 3 /H 4 receptors and mimicked by drugs containing an imidazole ring in their chemical structure and by imidazole itself. Taken together, our results show that in DU-145 cells histamine augments b 2 -adrenoceptor-induced cAMP independently of the activation of known his- tamine receptors. The effect may involve other mechanisms such as allosteric modulation of b 2 -adrenoceptors by the imidazole moiety of histamine. # 2006 Elsevier Inc. All rights reserved. * Corresponding autor at: Departamento de Neurociencias, Cinvestav, Apdo. postal 14-740, 07000 Me ´ xico, D.F., Mexico. Tel.: +52 555 061 3964; fax: +52 555 061 3754. E-mail address: jaarias@fisio.cinvestav.mx (J.-A. Arias-Montan ˜ o). available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/biochempharm 0006-2952/$ – see front matter # 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.bcp.2006.11.022