| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
The 5-HT_3 receptor (5-HT_3R), a ligand-gated, cation-selective ion channel, is thought to play a key role in the emetic reflex. 5-HT_3R antagonisis are effective in reducing the incidence of nausea and vomiting associated with inhalation anesthesia, but the underlying mechanism has not well been studied. We examined effects of three inhalation anesthetics, halothane, isoflurane and sevoflurane, on the 5-HT_3R-mediated current (I_<5HT3>) of cultured rat nodose ganglion cells using whole cell patch recording techniques.
Applications of either 5-HT or 2-methyl-5-HT,the selective 5-HT<@D23@>D2R agonist produced transient in ward currents (TICs) at the holding potentials of -50 to -60 mV in 42% (36/38) of neurons tested. The TIC reversed its polarity at 4(]SY.+-。[)2 mV (mean(]SY.+-。[)SD,n=8) and was completely blocked by ICS-205-930 (100nM), the 5-HT<@D23@>D2R antagonist (n=5). Thus the TIC was identified as the I<@D25HT3@>D2. Halothane at 0.8mM,equivalent to 2 MAC (minimum alveolar concentration), potentiated the I<@D25HT3@>D2 to 146(]SY.+-。[)16% to 146(]SY.+-。[)16% of the control response (n=4), whereas it depressed the I<@D25HT3@>D2 to 50(]SY.+-。[)15% of the control at 2.4mM (n=4). The I<@D25HT3@>D2 was potentiated to 125(]SY.+-。[)12% (n=4) of the control by isoflurane at 0.6mM (2MAC), but remained 90(]SY.+-。[)7% of the control at 1.7mM (n=4). Sevoflurane depressed the I<@D25HT3@>D2 dose-dependently without affecting the current-voltage relationship : the relative I<@D25HT3@>D2 was 67(]SY.+-。[)12% at 0.6 mM (2MAC,n=5) and 28(]SY.+-。[)10% at 1.7 mM (n=5).
These results suggest that halothane and isoflurane potentiate but sevo oflurane depresses the I_<5HT3> at the their clinical concentrations. The depressant action of sevoflurane on the 5-HT_3R may, therefore, bu beneficial in reducing the incidence of nansea and vomiting associated with inhalation anesthesia.
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