The inositol 1,4,5-trisphosphate (InsP3) receptor acts as an InsP3-gated Ca2+ release channel in a variety of cell types. Type 1 InsP3 receptor (IP3R1) is the major neuronal member of the IP3R family in the central nervous system, predominantly enriched in cerebellar Purkinje cells but also concentrated in neurons in the hippocampal CA1 region, caudate-putamen, and cerebral cortex. Here we report that most IP3R1-deficient mice generated by gene targeting die in utero, and born animals have severe ataxia and tonic or tonic-clonic seizures and die by the weaning period. An electroencephalogram showed that they suffer from epilepsy, indicating that IP3R1 is essential for proper brain function. However, observation by light microscope of the haematoxylin-eosin staining of the brain and peripheral tissues of IP3R1-deficient mice showed no abnormality, and the unique electrophysiological properties of the cerebellar Purkinje cells of IP3R1-deficient mice were not severely impaired.

Nonsteroidal anti-inflammatory drugs and acetaminophen are cyclooxygenase inhibitors commonly used as symptomatic medicines for myofascial pain syndrome. Using the selective inhibitors celecoxib and zaltoprofen, cyclooxygenase-2 has been shown to be involved in the initiation, but not the maintenance, of muscular mechanical hyperalgesia induced by lengthening contractions, which serves as a useful model for the study of myofascial pain syndrome. The effect of other cyclooxygenase-2 inhibitors, such as acetylsalicylic acid, ibuprofen, loxoprofen sodium, and acetaminophen, on muscular mechanical hyperalgesia during maintenance has not been studied. Here, we examined the analgesic effects of the nonsteroidal anti-inflammatory drugs and acetaminophen on the model. Consistent with previous studies, mechanical withdrawal threshold of the muscle was significantly decreased and reached its lowest level 24 h after lengthening contractions. Celecoxib had no effect on muscular mechanical hyperalgesia, when orally administered 24 h after lengthening contractions. In contrast, acetylsalicylic acid, ibuprofen, loxoprofen sodium, and acetaminophen increased the withdrawal threshold, which had decreased by lengthening contractions, in a dose-dependent manner. These results demonstrate the analgesic actions of nonsteroidal anti-inflammatory drugs and acetaminophen in the maintenance process of lengthening contraction-induced muscular mechanical hyperalgesia, which may occur through cyclooxygenase-2 independent mechanisms.

Body odours are generated from dead skin cells and secreted materials, such as sweat and sebum, through the metabolism of microorganisms living on the skin. Volatile steroids, key compounds in body odours, are also generated through the metabolism of microorganisms. These volatile steroids strengthen the intensity of the overall body malodour and are sensed differently by males and females. Females are more sensitive than males to volatile steroids, especially 5alpha-androst-16-en-3-one (androstenone). To regulate body odours that are especially unpleasant for women, we devised an androstenone-generation model using the metabolism of Corynebacterium xerosis, which is one of the bacteria living on the axillary skin. Using this model, we studied the suppressive effect of plant extracts on the generation of androstenone. We found that apricot kernel extract (AKE) had the most positive effect among the plant extracts to which we applied the model. However, although AKE did suppress androstenone generation, it did not show any bactericidal effect. Using the cell-free system, AKE also suppressed the generation of androstenone. In conclusion, we found that AKE suppressed the generation of androstenone, which is especially unpleasant for women, and the mechanism was not bactericidal but metabolic inhibition. The results of these studies provide new understanding of the regulation of androstenone, which, in turn, should lead to the development of novel deodorant systems.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage as a side effect. Acetaminophen, widely used as an analgesic and antipyretic drug, has gastroprotective effects against gastric lesions induced by absolute ethanol and certain NSAIDs. However, the mechanisms that underlie the gastroprotective effects of acetaminophen have not yet been clarified. In the present study, we examined the role and protective mechanism of acetaminophen on ibuprofen-induced gastric damage in rats. Ibuprofen and acetaminophen were administered orally, and the gastric mucosa was macroscopically examined 4 hours later. Acetaminophen decreased ibuprofeninduced gastric damage in a dose-dependent manner. To investigate the mechanisms involved, transcriptome analyses of the ibuprofen-damaged gastric mucosa were performed in the presence and absence of acetaminophen. Ingenuity pathway analysis (IPA) software revealed that acetaminophen suppressed the pathways related to cellular assembly and inflammation, whereas they were highly activated by ibuprofen. On the basis of gene classifications from the IPA Knowledge Base, we identified the following five genes that were related to gastric damage and showed significant changes in gene expression: interleukin-1b (IL-1b), chemokine (C-C motif) ligand 2 (CCL2), matrix metalloproteinase-10 (MMP-10), MMP-13, and FBJ osteosarcoma oncogene (FOS). Expression of these salient genes was confirmed using real-time polymerase chain reaction. The expression of MMP-13 was the most reactive to the treatments, showing strong induction by ibuprofen and suppression by acetaminophen. Moreover, MMP-13 inhibitors decreased ibuprofeninduced gastric damage. In conclusion, these results suggest that acetaminophen decreases ibuprofen-induced gastric mucosal damage and that the suppression of MMP-13 may play an important role in the gastroprotective effects of acetaminophen.