Histamine regulates the MAPK pathway via the H2 receptors in PANC-1 human cells

CRICCO GRACIELA; MARTIN GABRIELA; MEDINA VANINA; NUÑEZ MARIEL; GUTIERREZ ALICIA; COCCA CLAUDIA; BERGOC ROSA; RIVERA ELENA

13-17 of May, 2003, Amsterdam, Holland

Congreso; XXXII Annual Meeting of the European Histamine Research Society; 2003

HISTAMINE REGULATES MAPK PATHWAY VIA H2 RECEPTOR PANC-1 HUMAN CELLS. PANC-1 cells overexpress H1 and H2 histamine (Hi) receptors. In these cells, H2 receptors mediate cAMP production, inhibit cellular growth and arrest cell cycle in G0/G1 without inducing apoptosis but partially activating the differentiation program(1). We studied the interaction between H2 receptors, cAMP and MAPK pathways. We evaluated cell proliferation in the presence of 10 mM Hi (38%), 250 nM PKA inhibitor H89 (98%), 5 mM Forskolin (Fk, 45%), Fk+H89 (78%), p<0.05 vs control (100%). Fos, Myc and phosphoactivated p38 and ERKs expression was assessed by  immunoblottting. Fos was highly expressed but not modified by different treatments indicating that it is probably deregulated.  Myc expression was increased only when cells were incubated in 10% fetal calf serum supplemented medium and no change was observed when Hi, H2 agonist or Fk were employed. Hi and Fk mediated cell growth inhibition was correlated to a decrease in activated ERKs expression and to an increase in activated P38 expression. We conclude that in PANC-1 cells  cAMP production and PKA activation via H2 receptors may modulate MAPK pathway inhibiting cell proliferation through a negative balance between p38 and  ERKs. (1)   Martin G et al. Inflamm res 51(2002)1-7. This work was supported by grants form the University of Buenos Aires (B060) and SECYT (PICT 04656).