Studies on the mechanism of activation and deactivation of histidine decarboxylase

Abstract

In mice, histidine decarboxylase (HD) activity of liver was unaffected by pretreatment with substrate, l-histidine, or with histamine mixed with oil for slow absorption. Protein synthesis inhibitors (PSI) given during a 4-hr period not only blocked HD activation by endotoxin in spleen and lymph node, but reduced activity below the basal level. However, when PSI were started 4–5 hr after endotoxin, during the period of HD deactivation, they had no effect. In mice injected with Freund's adjuvant, and given PSI on day 3 (the time of maximal HD), HD activity of lung, liver and spleen was reduced, but not to subnormal levels; actinomycin D had little effect. Actinomycin given to endotoxin-treated mice in long-term (21–24 hr) experiments caused abnormally high HD levels in liver and lung. Short-term effects of PSI and actinomycin on in vitro HD activity were confirmed in vivo. Systematically injected PSI had no major effect on mouse skin HD: the latter is probably mainly in mast cells. Pretreatment with dibutyryl cyclic AMP, or azathioprine (a purine analog) failed to affect endotoxin activation of HD in lung and liver, respectively. Evidence that endotoxin activation of HD is triggered by release of loosely bound non-mast cell histamine was sought but not obtained. In adrenalectomized mice maintained on cortisol acetate, activation of muscle HD was less by noradrenaline than by adrenaline, but pretreatment with dibenzyline enhanced noradrenaline activation but decreased adrenaline activation. In adrenalectomized cortisol-maintained rats, noradrenaline activated muscle HD. In intact rats, the marked drop in lung HD caused by glucocorticoid treatment was unaffected by actinomycin. Significance of these data for mechanisms of HD activation and deactivation are discussed.