THE EFFECT OF HISTAMINE ON EPIDERMAL OUTGROWTH - ITS POSSIBLE DUAL ROLE AS AN INHIBITOR AND STIMULATOR

[摘要] The effect of histamine on pig epidermal cell outgrowths in vitro was studied. Histamine inhibited epidermal cell outgrowths (and mitosis). This inhibition was partially counteracted by a specific H2 antagonist, cimetidine. Inhibition was maximal at a histamine concentration of 10-4 M and was less at 10-3 M. Histamine concentrations respectively coincided with optimal concentrations for accumulating intracellular cAMP (via H2 receptors) and cGMP (via H1 receptors) in the same pig epidermal slice system. 4-Methyl-histamine, a pure H2 agonist, which only increased intracellular cAMP level but not cGMP level, caused a maximal outgrowth inhibition at 10-3 M. Attempts to counteract histamine effects due to cGMP accumulation by various H1 antagonists (so that 10-3 M histamine would have caused maximal outgrowth inhibition) were unsuccessful, since the addition of each H1 antagonist alone strongly inhibited outgrowth. Data suggested a dual role of histamine through the cyclic nucleotide system. Histamine inhibited epidermal cell growth by elevating intracellular cAMP level via an H2 receptor. Histamine at high concentrations (10-3 M) partially counteracted the inhibition by increasing cGMP via an H1 receptor.