Increase in histidine decarboxylase activity of rat skin following treatment with compound 48/80

Abstract

Repeated injections of rats with compound 48/80, a histamine liberator, results in a marked increase in histidine decarboxylase activity of the skin. The increase is roughly proportional to the duration of treatment. This eliminates activation of pre-existing histidine decarboxylase as a probable mechanism. The increase can be demonstrated in intact rats; therefore, rat skin histidine decarboxylase is an adaptive enzyme. It seems probable that 48/80 treatment leads to the production of new, resistant mast cells which are particularly active in forming histamine. This speculation is compatible with reports from other laboratories of histological studies on rats given 48/80. Implications of this finding are discussed.

Observations on the inhibition of histamine formation

“…The escape from inhibition with semicarbazide alone and the rebound in histamine formation on discontinuing effective inhibition could be explained by the assumption that a reduction in tissue histamine content adaptively elevates the HFC. It has in fact been demonstrated that depletion of rat skin histamine by 48/80 or polymyxin B concomitantly activates skin histidine decarboxylase (Schayer, Rothschild & Bizoni, 1959;Schayer & Ganley, 1959). These circumstances prompted the following experiment.…”

Increase in Brain Pyridoxal Phosphate by Chlorpromazine

“…On the other hand, Vitamin B6 deficiency states reduced the activity of apocysteine sulfinate de carboxylase [Hope, 1955] and threonine dehydrase [Bergeret et al, 1955]. In addition, the activity of L-aromatic amino acid decarbo xylase was inhibited by using 5-hydroxytryptophan fBuxton and , 1956;Weissbach et al, 1957], dopa [ West, 1953 andSourkes et al, 1960] and histidine [Schayer et al, 1959] as substrates. The addition of PLP restores the activity of the enzyme in vitro.…”

Histamine‐forming capacity of multiplying cells

“…that histidine decarboxylase is adaptive in nature (Schayer, Rothschild & Bizony, 1959). Attempts to recognize the significance of the elevation of HFC found in physiological and pathological circumstances have followed two currents of thought.…”