HISTAMINE-RECEPTORS IN AN EXPERIMENTAL MAMMARY-CARCINOMA

An experimental mammary carcinoma was induced in Sprague-Dawley rats b y the ip administration of N-nitroso-N-methylurea (NMU) in three doses of 50 mg/kg. In order to study the expression of histamine receptors in these experimental tumors, the presence of specific binding sites f or histamine was studied. Using [H-3]-histamine as a radioligand, two specific binding sites were characterized on the cell membrane. The fi rst site, of high affinity, Kd = 4 +/- 2 nM, was further characterized as an H2 type using [H-3]-cimetidine and [H-3]-tiotidine as radioliga nds and by displacement experiments with different histamine agonists and antagonists. The second one of low affinity, Kd = 35 +/- 14 nM, ne eds further characterization. The determination of cAMP levels showed that histamine and the H2 agonist dimaprit, produced a significant dec rease in the nucleotide concentration 6 minutes after stimulation, in a response that was specifically abolished by H2 antagonists. Based on these results, we conclude that neoplastic cells from NMU induced tum ors express H2 histamine membrane receptors which are coupled to a tra nsductional pathway different from cAMP production, which may be invol ved in the regulation of tumor growth.