Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.
The immunohistochemical localization of glutamate transporter GLAST in the developing mouse cochlea was studied at different ages between 0 and 30 days after birth (DAB). In the adult mouse cochlea, intense GLAST-like immunoreactivity was found in the supporting cells adjacent to the inner hair cells of the organ of Corti, the type II and suprastrial fibrocytes of the cochlear lateral wall, the fibrocytes of the spiral limbus and the satellite cells surrounding the spiral ganglion cells. At 0 DAB, weak GLAST-like immunoreactivity was found in the supporting cells around the immature inner hair cells. Immature fibrocytes in the cochlea were also positively immunostained. At 3 DAB, weak immunostaining of GLAST appeared in the immature satellite cells in the spiral ganglion. The GLAST-like immunoreactivity in the supporting cells around the inner hair cells, in the fiborocytes in the spiral ligament and the spiral limbus and in the satellite cells in the spiral ganglion increased progressively during the second postnatal week, and reached the adult level at 15 DAB. This time course correlates with the electrophysiological onset and maturation of the mouse auditory function, which is mediated by glutamatergic neurotransmission. These results suggest that the expression of GLAST may be needed for the efficient removal and metabolism of the released glutamate in the cochlea and may play important roles in the onset and maturation of the auditory system.
Flavonoid-rich ethanol extracts of licorice root have sedative and anxiolytic effects. Glabridin is a major flavonoid component from licorice which we evaluated by examining GABA responses in acutely isolated dorsal raphe neurons of the rat. Neurons were recorded with patch-clamp methods at a holding potential of - 50 mV. Glabridin potentiated GABA-induced responses by positively modulating GABAA receptor responses with different concentration range. GABA (2 × 10(-6) M)-evoked currents were potentiated in a stepwise pattern increasing glabridin concentration. Between 10(-12) and 10(-8) M glabridin increased GABA responses by about 140 % of the control. At concentrations above 10(-7) M, a much larger, dose-dependent potentiation occurred before reaching a plateau at 3 × 10-6 M glabridin. A hypnotic drug, zolpidem, also induced biphasic concentration-potentiation relationship. The glabridin potentiation ratio was 2.2 times larger than the maximum potentiation to the benzodiazepine receptor full agonist diazepam. Benzodiazepine receptor antagonist, flumazenil (3 × 10(-7) M), failed to inhibit glabridin (3 × 10(-7) M)-induced potentiation. This result implies that glabridin may exhibit sedative and hypnotic effects by potentiating GABAergic inhibition in dorsal raphe neurons by GABAA receptor actions.
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