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Histamine and specific histamine receptors increase normal cholangiocyte growth via differential mechanisms
Author(s) -
Francis Heather,
Gaudio Eugenio,
Ueno Yoshiyuki,
Venter Julie,
Onori Paolo,
DeMorrow Sharon,
Alpini Gianfranco
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1000.3
Subject(s) - cholangiocyte , histamine , phosphorylation , endocrinology , medicine , chemistry , signal transduction , mapk/erk pathway , receptor , microbiology and biotechnology , biology
Normal cholangiocytes proliferate after injury. Histamine (HA) interacts with four receptors (H1–H4). We have shown that histamine receptors (HRs) induce differential effects in cholangiocytes. We evaluated: (i) HR expression, (ii) chronic effects of HA or specific HRs in normal rats (NR) and (iii) signaling mechanisms. HR expression was evaluated in cholangiocytes and cholangiocyte cultures (NRC). In vivo , NR were treated with HA or selected HR agonists: H1, HTMT dimaleate; H2, amthamine dihydrobromide; RAMH; H4, clobenpropit or NaCl. Cholangiocyte growth was evaluated by: (i) immunohistochemistry in liver sections and (ii) PCNA expression. NRIC were treated with HA or selected HR agonists. We measured growth, IP 3 and cAMP levels and phosphorylation of PKA and ERK1/2. HRs are found in NR and NRC. Administration of HA or H1 and H2 (but not H3 or H4) to NR increased cholangiocyte growth compared to NR + NaCl. In vitro , HA and H1HR increased growth (via Ca 2+ signaling), IP 3 and ERK1/2 phosphorylation. HA and H2HR stimulation increased growth (via PKA signaling), cAMP and phosphorylation of PKA and ERK 1/2. H3 and H4 had no effect. HA induces normal cholangiocyte growth. Activation of specific HRs modulates growth via independent mechanisms. Stimulatory (H1/H2) and inhibitory (H3/H4) effects by HRs may be important in the regulation of cholangiocyte growth/loss related to cholangiopathies.