N-Acetyl-p-aminophenol (APAP/acetaminophen) is a widely used analgesic/antipyretic with weaker inhibitory effects on cyclooxygenase compared to those of non-steroidal anti-inflammatory drugs. The effect of APAP is mediated by its metabolites, N-arachidonoyl-phenolamine and N-acetyl-p-benzoquinone imine, which activate transient receptor potential (TRP) channels, including TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or cannabinoid receptor type 1. However, the exact molecular mechanism underlying the cellular actions of APAP remains unclear. Recently, we observed that APAP promotes cell migration through TRPV4; in this study, we examined the effect of APAP on Ca 2þ-channel activity of TRPV4. In the rat cell line PC12 expressing TRPV4, GSK1016790A (GSK), a TRPV4 agonist, stimulated an increase in [Ca 2þ ] i ; these effects were abrogated by HC-067047 treatment. This GSK-induced Ca 2þ entry through TRPV4 was inhibited by APAP in a dose-dependent manner, whereas APAP alone did not affect [Ca 2þ ] i. The specificity of the effect of APAP on TRPV4 was further confirmed using HeLa cells, which lack endogenous TRPV4 but stably express exogenous TRPV4 (HeLa-mTRPV4). GSK-induced [Ca 2þ ] i elevation was only observed in HeLa-mTRPV4 cells compared to that in the control HeLa cells, indicating the specific action of GSK on TRPV4. APAP dosedependently suppressed this GSK-induced Ca 2þ entry in HeLa-mTRPV4. However, it is unlikely that the metabolites of APAP were involved in these effects as the reaction in this study was rapid. The results suggest that APAP suppresses the newly identified target TRPV4 without being metabolized and exerts antipyretic/analgesic and/or other effects on TRPV4-related phenomena in the body. The effect of APAP on TRPV4 was opposite to that on TRPV1 or TRPA1, as the latter is activated by APAP.

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Intravenous sedation (IVS) is commonly used to complete dental treatment for uncooperative pediatric patients. Propofol (PRO) is widely used for IVS because of its short context sensitive half-time and amnestic effect. However, administering PRO to patients who have a history of egg anaphylaxis is still somewhat controversial. The evidence that supports the potential risks for allergic reactions following PRO use in patients with egg allergies is limited with some anesthesiologists recommending against its use in these patients. Alternative drug regimens for procedural sedation in this population are therefore desirable. Dexmedetomidine (DEX), a selective α-2 agonist, has antianxiety and sedative properties and has been widely used not only for procedural sedation with mild inhibitory effects on respiration but also during minor surgeries for its analgesic effect. In this paper, we describe the successful administration of a combination of DEX and low-dose midazolam (MDZ) for sedation in an uncooperative pediatric patient. Both DEX and MDZ have been reported as safe and useful sedatives for dental treatment, and their combination may provide a helpful option for IVS of pediatric patients for whom PRO is not preferred.

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Bone matrix protein osteocalcin (OC) was recently reported to support the development of learning and memory and also prevent anxiety-like behaviors in mice. Although the mechanism through which OC affects systemic energy expenditure and glucose homeostasis has been relatively well studied, the direct actions of OC on neurons in detail are still uncovered. Therefore, we here investigated the effect of OC on neurons using rat pheochromocytoma cell line PC12, with special reference to the neurite outgrowth, cell proliferation and survival, as well as intracellular signaling. The number of PC12 cells cultured for four days in the presence of 5 to 50 ng/mL of OC was increased compared to the cells cultured in the absence of OC. The length, but not the number of NGF-induced neurite outgrowth was enhanced by OC. NGF-induced phosphorylation of Akt and ERK was both affected by pretreatment of the cells with OC. RT-PCR analysis for candidates of OC receptor revealed that mRNA expression of Gpr158, but not Gprc6a, was detected in PC12 cells. These results suggested that OC may exerts direct effect on cell growth and differentiation by binding to Gpr158 and modulation of downstream intracellular signaling. Poster Sessions