Atypical association of H1 and H2 histamine receptors with signal transduction pathways during multistage mouse skin carcinogenesis.
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.
Fitzsimons
C
C
Laboratorio de Radiosótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Molinari
B
B
Duran
H
H
Palmieri
M
M
Davio
C
C
Cricco
G
G
Bergoc
R
R
Rivera
E
E
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002452:Cell Count; D002927:Cimetidine / Q000031:analogs & derivatives / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006634:Histamine H1 Antagonists / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000378:metabolism; D006868:Hydrolysis; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism; D011738:Pyrilamine / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000502:physiology*; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000502:physiology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D013755:Tetradecanoylphorbol Acetate
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010716:Phosphatidylinositols; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D015127:9,10-Dimethyl-1,2-benzanthracene; D002927:Cimetidine; D000242:Cyclic AMP; C023990:tiotidine; D011738:Pyrilamine; D013755:Tetradecanoylphorbol Acetate