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

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.