von Kugelgen I, Starke K
Pharmakologisches Institut, Universität Freiburg, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):46-54. doi: 10.1007/BF00168915.
Activation of ionotropic but not metabotropic glutamate receptors causes an indirect inhibition of the release of noradrenaline in slices of rabbit brain cortex. The inhibition is mediated by adenosine which activates presynaptic adenosine A1-receptors. The present study characterizes the ionotropic receptor types through which glutamate itself produces this indirect inhibition. Rabbit brain cortex slices were preincubated with [3H]-noradrenaline, superfused with medium containing desipramine (1 microM) and stimulated electrically by trains of 6 pulses at 100 Hz. Glutamate (100-3000 micro M) reduced the electrically evoked overflow of tritium by up to 58%. The effect did not differ 20 min and 60 min after addition of glutamate. Adenosine deaminase (1 U ml-1) as well as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 30 microM) and D-gamma-glutamylamino-methanesulfonate (GAMS; 30 micro M), both of which block kainate receptors, attenuated the glutamate-induced inhibition. The NMDA receptor antagonist 2-amino-5-phosphonopentanoate (AP5; 100 micro M) and the AMPA receptor antagonist 6-nitro-7-sulfamoylbenzo(f)-quinoxaline-2,3-dione (NBQX; 30 micro M) did not change the effect of glutamate. Given alone, CNQX and GAMS, but not AP5 and NBQX, slightly increased the evoked overflow of tritium; the increases were abolished in the presence of adenosine deaminase. The results indicate that activation of kainate but not NMDA and AMPA receptors is involved in the indirect, adenosine-mediated inhibition by exogenous glutamate of the release of noradrenaline in rabbit brain cortex slices. Moreover, as shown by the increase caused by CNQX and GAMS, endogenous excitatory amino acids inhibit the release of noradrenaline through the kainate receptor-adenosine mechanism and thus contribute to the purinergic inhibitory control of noradrenaline release in the brain.
离子型而非代谢型谷氨酸受体的激活会间接抑制兔脑皮质切片中去甲肾上腺素的释放。这种抑制作用由腺苷介导，腺苷可激活突触前腺苷A1受体。本研究对谷氨酸自身产生这种间接抑制作用所通过的离子型受体类型进行了表征。将兔脑皮质切片与[3H] - 去甲肾上腺素预孵育，用含地昔帕明（1 microM）的培养基进行灌流，并以100 Hz的频率施加6个脉冲的电刺激。谷氨酸（100 - 3000 microM）可使电诱发的氚溢出减少高达58%。添加谷氨酸后20分钟和60分钟，该效应无差异。腺苷脱氨酶（1 U/ml - 1）以及6 - 氰基 - 7 - 硝基喹喔啉 - 2,3 - 二酮（CNQX；30 microM）和D - γ - 谷氨酰胺甲磺酸盐（GAMS；30 microM），二者均能阻断海人酸受体，可减弱谷氨酸诱导的抑制作用。NMDA受体拮抗剂2 - 氨基 - 5 - 膦酰戊酸（AP5；100 microM）和AMPA受体拮抗剂6 - 硝基 - 7 - [磺酰胺基]苯并[f]喹喔啉 - 2,3 - 二酮（NBQX；30 microM）并未改变谷氨酸的作用。单独给予时，CNQX和GAMS，但不是AP5和NBQX，会使诱发的氚溢出略有增加；在腺苷脱氨酶存在的情况下，这种增加被消除。结果表明，海人酸受体而非NMDA和AMPA受体的激活参与了外源性谷氨酸对兔脑皮质切片中去甲肾上腺素释放的间接腺苷介导的抑制作用。此外，如CNQX和GAMS所引起的增加所示，内源性兴奋性氨基酸通过海人酸受体 - 腺苷机制抑制去甲肾上腺素的释放，从而有助于大脑中去甲肾上腺素释放的嘌呤能抑制性控制。
