- 作者: Nien-Tzu Keng, Hsun-Hsun Lin, Huei-Ru Lin, Wei-Kung Hsieh, Chih-Chia Lai
- 作者服務機構: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background: Acute exposure of ethanol (alcohol) inhibits NMDA receptor function.
Our previous study showed that acute ethanol inhibited the pressor responses induced by
NMDA applied intrathecally; however, prolonged ethanol exposure may increase the levels of
phosphorylated NMDA receptor subunits leading to changes in ethanol inhibitory potency on
NMDA-induced responses. The present study was carried out to examine whether acute
ethanol exposure influences the effects of ketamine, a noncompetitive NMDA receptor
antagonist, on spinal NMDA-induced pressor responses.
Methods: The blood pressure responses induced by intrathecal injection of NMDA were
recorded in urethane-anesthetized rats weighing 250-275 g. The levels of several
phosphorylated residues on NMDA receptor GluN1 and GluN2B subunits were determined
by western blot analysis.
Results: Intravenous injection of ethanol or ketamine inhibited spinal NMDA-induced
pressor responses in a dose-dependent and reversible manner. Ketamine inhibition of
NMDA-induced responses was synergistically potentiated by ethanol when ethanol was
applied just before ketamine. However, ketamine inhibition was significantly reduced when
applied at 10 min after ethanol administration. Western blot analysis showed that intravenous
ethanol increased the levels of phosphoserine 897 on GluN1 subunits (pGluN1-serine 897),
selectively phosphorylated by protein kinase A (PKA), in the lateral horn regions of spinal
cord at 10 min after administration. Intrathecal administration of cAMPS-Sp, a PKA activator,
at doses elevating the levels of pGluN1-serine 897, significantly blocked ketamine inhibition
of spinal NMDA-induced responses.
Conclusions: The results suggest that ethanol may differentially regulate ketamine
inhibition of spinal NMDA receptor function depending on ethanol exposure time and the
resulting changes in the levels of pGluN1-serine 897. - 中文關鍵字: --
- 英文關鍵字: alcohol, ketamine, NMDA receptor, PKA, phosphorylation, sympathetic neuron