H4 receptorª²mediated stimulation of histamine on AtTª²20 cells to release ACTH

    MENG Jia, XIE Jianª²Jun, YANG Tieª²Hong, WANG Haiª²Fang, LI Mingª²Kai, HU Jing, LUO Xiaoª²Xing

    Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi¬ðan 710033, China

     ¡¾Abstract¡¿ AIM: To clarify the subtype of histamine (HA) receptor which mediates Adrenocorticotropic Hormone(ACTH) release from mouse anterior pituitary tumor cell line AtTª²20. METHODS: ELISA assay was used to determine the effects of a variety of histamine receptor subtypeª²specific agonists and antagonists on ACTH release from AtTª²20 cells. The expression of H4 receptor mRNA on AtTª²20 cells was detected by RTª²PCR and the PCR product was sequenced. RESULTS: ¢Ù HA (10ª²8 mol/L) significantly accelerated the release of ACTH (pmol/L) from AtTª²20 cells (5.7¡À1.1 vs 2.7¡À0.6 in control, P<0.01). The histamine H1ª²receptor specific antagonist Chlorpheniramine (5.7¡À0.7) and histamine H2ª²receptor specific antagonist Ranitidine (5.8¡À1.0) did not inhibit the effect of HA. ¢Ú The same as HA, histamine H3ª² and H4ª²receptor agonist Rª²(¦Á)ª²Methylhistamine (10-7 mol/L) increased the release of ACTH from AtTª²20 cells (5.9¡À1.3). ¢Û H4ª²receptor specific antagonist JNJ777120 (1ª²[(5ª²Chloroª²1Hª²indolª²2ª²yl)carbonyl]ª² 4ª²methylpiperazine) demonstrated a concentrationª²dependent inhibitory effect on the increasing ACTH secretion induced by HA, and the effect of HA was totally abolished by JNJ777120 at 10-5 mol/L. ¢Ü RTª²PCR confirmed that AtTª²20 cells presented an endogenous expression of H4ª²receptor mRNA. CONCLUSION: HA stimulates the release of ACTH from AtTª²20 cells through H4 receptor mediation. ......