Induction of the Histamine-Forming Enzyme Histidine Decarboxylase in Skeletal Muscles by Prolonged Muscular Work: Histological Demonstration and Mediation by Cytokines.

Recent studies suggest that histamine-a regulator of the microcirculation-may play important roles in exercise. We have shown that the histamine-forming enzyme histidine decarboxylase (HDC) is induced in skeletal muscles by prolonged muscular work (PMW). However, histological analysis of such HDC induction is lacking due to appropriate anti-HDC antibodies being unavailable. We also showed that the inflammatory cytokines interleukin (IL)-1 and tumor necrosis factor (TNF)-α can induce HDC, and that PMW increases both IL-1α and IL-1ß in skeletal muscles. Here, we examined the effects (a) of PMW on the histological evidence of HDC induction and (b) of IL-1ß and TNF-α on HDC activity in skeletal muscles. By immunostaining using a recently introduced commercial polyclonal anti-HDC antibody, we found that cells in the endomysium and around blood vessels, and also some muscle fibers themselves, became HDC-positive after PMW. After PMW, TNF-α, but not IL-1α or IL-1ß, was detected in the blood serum. The minimum intravenous dose of IL-1ß that would induce HDC activity was about 1/10 that of TNF-α, while in combination they synergistically augmented HDC activity. These results suggest that PMW induces HDC in skeletal muscles, including cells in the endomysium and around blood vessels, and also some muscle fibers themselves, and that IL-1ß and TNF-α may cooperatively mediate this induction.

Effect of a nutritive-tonic drink on stress-induced serum glucocorticoid in the mouse.

We evaluated stress during "restraint with gnawing (R+G+)" and "restraint without gnawing (R+G-)" in a mouse system. R+G- induced a higher serum glucocorticoid level than R+G+. Zena F-III (a nutritive-tonic drink prescribed as "Kampo", a traditional Japanese medicine with its origin in Chinese medicine) reduced the glucocorticoid elevation in R+G+, but not in R+G-. These results support the hypotheses that (i) activity, such as gnawing, which potentially leading to escape from distress, reduces the severity of emotional distress and (ii) Zena F-III reduces the severity of mental or emotional fatigue, or increases motivation, in a stressful situation that the animal can manage itself.

Elevation of histidine decarboxylase activity in the stomach of mice by ulcerogenic drugs.

Histamine is involved in the development of gastric lesions. To examine the contribution of the histamine-forming enzyme, histidine decarboxylase, to drug-induced gastric lesions, we compared the effects of aspirin, indomethacin and dexamethasone on histidine decarboxylase activity in mice. Administration of these drugs, orally or intraperitoneally, elevated histidine decarboxylase activity in the stomach but not in the liver, lung or spleen, dexamethasone being the most potent. In contrast, acetaminophen (a non-ulcerogenic drug) was inactive. These results and our previously reported findings (elevation of histidine decarboxylase activity by lipopolysaccharide, interleukin-1 and tumour necrosis factor, and by different types of stress) suggest that an elevation of histidine decarboxylase activity in the stomach may be a common feature of the responses to ulcerogenic stimuli. The possible participation of histidine decarboxylase in gastric lesions is discussed on the basis of the known actions of histamine, our findings and the effect of histamine H(2) receptor antagonists on histidine decarboxylase activity.

Gnawing behavior of a mouse in a narrow cylinder: a simple system for the study of muscle activity, fatigue, and stress.

When a mouse is put into a cylinder too narrow for it to turn (its front end being blocked with a thin plastic strip), the mouse gnaws away the plastic to escape. Hence, the weight reduction in the plastic can be used as an index of 'gnawing activity (GA).' GA was high at first, but decreased with time. Training augmented GA, but not the activity of the histamine-forming enzyme (histidine decarboxylase [HDC]: a proposed marker of muscle fatigue) in the masseter muscle. In trained mice, GA was higher at night than in the daytime, and was decreased by starvation. In mice prevented from reaching the strip, the elevation of serum cortisol was greater than that seen in mice able to gnaw at it. As such gnawing is a form of voluntary behavior, these results suggest that our experimental system may be useful for (i) the quantitative study of voluntary muscle activity associated with physical or mental fatigue or motivation, and (ii) the study of an animal's response to stress when it has, or alternatively does not have, an apparent way of escape.