Activation of the human histamine H 2 receptor is linked to cell proliferation and c- fos gene transcription

• Published in: American Journal of Physiology: Cell Physiology Vol. 273; no. 6; pp. C2037 - C2045
• Main Authors: Wang, L-D, Hoeltzel, M, Butler, K, Hare, B, Todisco, A, Wang, M, Del Valle, J
• Format: Journal Article
• Language: English
• Published: United States 01.12.1997
• Subjects: signal transduction; biogenic amine receptor
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.1997.273.6.C2037

We examined whether histamine could regulate cell proliferation and expression of the early response gene c- fos in HEK-293 cells stably transfected with the human H receptor (HEK-H ). Histamine stimulated [ H]thymidine incorporation [50% effective concentration (EC ) = 3.6 × 10 M] in HEK-H cells in a cimetidine-sensitive manner and increased c- fos mRNA in a time-dependent fashion, reaching maximal induction after 30 min. Histamine induced luciferase activity in HEK-H cells transiently transfected with a construct containing the luciferase reporter gene ( Luc) coupled to the serum response element (SRE) of the c- fos gene promoter (EC = 1.5 × 10 M) or a plasmid containing the SRE core fragment (bases -320 to -298). The protein kinase C (PKC) inhibitor staurosporine and long-term pretreatment of HEK cells with phorbol ester inhibited the effect of histamine on PKC activation, SRE- Lucactivity, and [ H]thymidine incorporation. We have demonstrated that activation of the human H receptor can lead to induction of c- fos gene transcription and cell proliferation through a PKC-dependent mechanism.