The human histamine H2 receptor regulates c-jun and c-fos in a differential manner

L. D. Wang, M. Wang, A. Todisco, E. Grand, J. del Valle
2000 American Journal of Physiology - Cell Physiology  
The human histamine H 2 receptor regulates c-jun and c-fos in a differential manner. Am J Physiol Cell Physiol 278: C1246-C1255, 2000.-Previously, we demonstrated that activation of the human H 2 receptor (hH 2 R) leads to an increase in c-fos transcription and cell proliferation. The purpose of these studies was to examine whether hH 2 R regulates c-jun expression and, if so, explore the mechanisms by which it does so. Histamine induced an increase in c-jun mRNA in human embryonic kidney cells
more » ... stably transfected with the hH 2 R (maximal effect: 554.6 Ϯ 86.8% of control). The protein kinase C (PKC) inhibitors staurosporine (10 Ϫ6 M) and GF-109203X (10 Ϫ6 M) significantly inhibited histamine-stimulated c-fos mRNA while not altering c-jun expression. The protein kinase A (PKA) pathway inhibitors Rp-cAMP and protein kinase inhibitor did not affect the action of histamine on c-jun or c-fos mRNA. Histamine (10 Ϫ4 M) stimulated extracellularly regulated kinase 2 tyrosine phosphorylation. The specific inhibitor of the mitogen-activated protein (MAP) kinase pathway, PD-98059 (5 ϫ 10 Ϫ5 M), significantly inhibited histamine-induced c-fos and c-jun mRNA. Of interest, the p70 S6 kinase inhibitor rapamycin (10 Ϫ6 M) but not wortmannin decreased histamine-stimulated c-jun mRNA by 58.5 Ϯ 12% (mean Ϯ SE, n ϭ 4) while not significantly altering c-fos message. Histamine (10 Ϫ4 M) also led to an ϳ4.5-fold increase in Jun NH 2 -terminal kinase activity in a PKC-, PKA-, and MAP kinase-independent but rapamycinsensitive manner. Our findings suggest that histamine stimulates both c-fos and c-jun mRNA in a differential manner. PKC is involved in histamine-mediated c-fos activation, whereas p70 S6 kinase is important for linkage of this receptor to c-jun. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
doi:10.1152/ajpcell.2000.278.6.c1246 pmid:10837353 fatcat:kkyvimw3wbedjpjgabhfilcidu