Michio Kurachi

Analysis of the spontaneous scratching behavior by NC/Nga mice: a possible approach to evaluate antipruritics for subjects with atopic dermatitis

We investigated the spontaneous scratching by NC/Nga mice to design a new method for evaluating the itch of subjects with atopic dermatitis. The numbers of scratchings in various strains of mice were classified based on the duration of the scratching. Prolonged scratching was frequent in skin-lesioned NC/Nga mice, but not in ICR, BALB/c and non-lesioned NC/Nga mice. Pretreatment with dexamethasone or tacrolimus significantly suppressed long-duration scratching in NC/Nga mice but did not suppress short-duration scratching induced by ovalbumin active cutaneous anaphylaxis in BALB/c mice and in ICR mice subcutaneously injected with histamine. In contrast, pretreatment with chlorpheniramine or ketotifen significantly suppressed short-duration scratching induced by ovalbumin active cutaneous anaphylaxis in BALB/c mice and in ICR mice subcutaneously injected with histamine, but not long-duration scratching seen in NC/Nga mice. These findings indicate that the mechanism of spontaneous scratching in NC/Nga mice differs from that induced by several pruritogen injections. This new method shows good correlation with the therapeutic activity of drugs in cases of atopic dermatitis in humans and may serve as a useful model for evaluating antipruritic drugs and for studying mechanisms involved in atopic dermatitis.

Effects of high‐affinity nerve growth factor receptor inhibitors on symptoms in the NC/Nga mouse atopic dermatitis model

Background  Nerve growth factor (NGF) is an important substance in the skin, where it modulates nerve maintenance and repair. However, the direct link between NGF and pruritic diseases such as atopic dermatitis is not yet fully understood. Our previous study showed that NGF plays an important role in the pathogenesis of atopic dermatitis‐like skin lesions in NC/Nga mice. NGF mediates its effects by binding to two classes of transmembrane receptors, a high‐affinity receptor (tropomyosin‐related kinase A, TrkA) and a low‐affinity receptor (p75).

Dopamine D2 receptors and spinal cord excitation in mice

Spinal cord excitation was induced in mice by morphine and the effects of dopamine D1 and D2 receptor antagonists on the Straub tail reaction were investigated. The dopamine D2 receptor antagonist, sulpiride (25-100 mg/kg i.p.), or haloperidol (0.25-1.0 mg/kg dose dependently inhibited the Straub tail reaction induced by subcutaneously injected morphine. A low dose of apomorphine (50 micrograms/kg s.c.) also reduced the Straub tail reaction. The dopamine D1 receptor antagonist, SCH-23390 (25-100 micrograms/kg i.p.), had no significant effect. Sulpiride (50 mg/kg i.p.) significantly inhibited the Straub tail reaction induced by intrathecally injected morphine (6 microgram/mouse). Intrathecal injection of apomorphine (12.5-25 micrograms/mouse) induced the Straub tail reaction dose dependently. The Straub tail reaction induced by intrathecally injected apomorphine was significantly inhibited by sulpiride. SCH-23390 had no significant effect on the Straub tail reaction induced by intrathecally injected morphine or apomorphine. These results support the proposal that the dopamine response involved in the Straub tail reaction is mediated by postsynaptic dopamine D2 receptors in the spinal cord of mice.

A method to induce stable atopic dermatitis-like symptoms in NC/Nga mice housed with skin-lesioned mice.

Background  Itching is a characteristic symptom in various forms of dermatosis, especially atopic dermatitis; consequently it is a major diagnostic criterion. All features are similar to events seen in patients, hence NC/Nga mice are considered to be a suitable model of human atopic dermatitis. However, there were data spreads in commencing time and the degree of skin lesions in NC/Nga mice.

5-HT3 receptor antagonists inhibit the response of κ oploid receptors in the morphine-reduced straub tail

Abstract We used the morphine-induced Straub tail to examine the actions of a 5-HT3 receptor antagonist and κ opioid receptor agonist. The κ opioid receptor agonist, U-50,488H (4–16 mg/kg i.p.), produced a dose-related inhibition of the tail elevation induced by morphine (10 mg/kg s.c.) in ICR male mice. ICS-205-930 (3 and 10 mg/kg i.p.) and zacopride (0.3 and 1 mg/kg i.p.), 5-HT3 receptor antagonists, attenuated the inhibitory effect of U-50,488H in a dose-dependent manner. ICS-205-930 and zacopride did not inhibit the morphine-induced Straub tail. These observations suggest that the actions of κ opioid receptors may be modulated by 5-HT3 receptors in the morphine-induced Straub tail.

Effect of an Orally Ingested Mugwort and Mushroom Extract Mixture on Urine Odor from Aged Mice

We had previously found that male mice could be trained to discriminate between the urine odor of aged and young adult (adult) mice. We hypothesized that these odors that characterized the older animals might be inhibited by a mixture of extracts (AAM) of mugwort and mushroom, because previous studies have indicated that these extracts could be used to reduce the intensity of unpleasant body odors. The findings of this chemical study strongly suggest that the AAM function helped to modify the aged mouse urine odor so that it more closely resembled the smell of urine from younger mice. Based on the results of the chemical studies, a set of behavioral experiments were therefore conducted. The results of three sets of generalization trials also strongly supported the results of the chemical studies. Togethers, these results suggest that ingested AAM decreased the intensity of odors associated with aging in mice.

Inhibitory Mechanism of Taurine on the Platelet-Derived Growth Factor BB-Mediated Proliferation in Aortic Vascular Smooth Muscle Cells

Platelet-derived growth factor-BB (PDGF-BB) is involved in the development of atherosclerosis in conjunction with the migration and the proliferation of vascular smooth muscle cells. PDGF-BB is produced by activated macrophages, smooth muscle cells and endothelial cells, or released from platelets, and its expression is increased in atherosclerotic lesions1,2. Thus, PDGF-BB is thought to play a critical role for the intimai thickening in the lesions of atherosclerosis.

Suppression of bronchial response to platelet activating factor following taurine administration.

Platelets contain a high level of taurine (10), and accumulate this neutral amino acid by an energy-dependent process (7). Taurine inhibits the aggregation induced by ADP (1), and hence is thought to modulate the platelet function.