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Inflammation Research

, Volume 46, Issue 8, pp 292–298 | Cite as

Atypical association of H1 and H2 histamine receptors with signal transduction pathways during multistage mouse skin carcinogenesis

  • C. Fitzsimons
  • B. Molinari
  • H. Duran
  • M. Palmieri
  • C. Davio
  • G. Cricco
  • R. Bergoc
  • E. Rivera

Abstract.

Objective: In the present work we studied the association of histamine receptors with second messengers during multistage carcinogenesis in Sencar mice skin.¶Methods: 96 Sencar female mouse, divided into six groups were used. Tumors appeared only in the 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted group. Control groups received only TPA, or acetone or no treatment at all. Periodically during the promotion period, cAMP and inositol phosphate production were measured after stimulation with H1 or H2 agonists in samples from all groups.¶Results: In non-treated skin, H1 receptors were coupled to phosphatidylinositol hydrolysis and H2 receptors mediated cAMP production. Conversely, in tumors H2 receptors were associated with phosphatidylinositol hydrolysis and H1 mediated a rise in cAMP levels. The skin among tumors and the skin from all control groups maintained the same coupling as non-treated skin. An increase in mast cell number, with a homogeneous subepithelial distribution and marked phenotypic changes, was also observed in promoted skin.¶Conclusions: These findings indicate an atypical association of histamine receptors with second messengers that could be a critical feature for the postulated action of histamine in tumor growth.

Key words: Histamine receptors — Inositol phosphates — cAMP — Mouse skin carcinogenesis 

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Copyright information

© Birkhäuser Verlag, Basel, 1997

Authors and Affiliations

  • C. Fitzsimons
    • 1
  • B. Molinari
    • 2
  • H. Duran
    • 2
  • M. Palmieri
    • 3
  • C. Davio
    • 1
  • G. Cricco
    • 1
  • R. Bergoc
    • 1
  • E. Rivera
    • 1
  1. 1.Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina, Fax +54 1 962 5341, e-mail: rivera@labrad.uba.arAR
  2. 2.Departamento de Radiobiología, Comisión Nacional de Energía Atómica, Laboratorio Tandar, Av. Gral Paz y Constituyentes, 1464 Pcia. de Buenos Aires, ArgentinaAR
  3. 3.Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, ArgentinaAR

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