Mayer A, Limberger N, Starke K
Pharmakologisches Institut der Universität, Freiburg i. Br., Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Dec;338(6):632-43. doi: 10.1007/BF00165627.
Slices of rabbit brain were field-stimulated either by single electrical pulses or by trains of 4 or 8 pulses at 1 or 100 Hz in order to study transmitter release patterns and the autoinhibition of transmitter release. The slices were preincubated with 3H-noradrenaline (cortex), 3H-dopamine (caudate nucleus) or 3H-choline (caudate nucleus). Slices preincubated with 3H-noradrenaline were superfused with medium containing desipramine 1 mumol/l. The overflow of tritium elicited by single pulses amounted to 0.19% of the tritium content of the tissue. The overflow elicited by 4 pulses/1 Hz was similar, whereas that elicited by 4 pulses/100 Hz was 5.1-fold higher. Yohimbine 10-1000 nmol/l increased up to 2.5-fold the overflow evoked by 4 pulses/1 Hz but did not change the overflow evoked by single pulses or 4 pulses/100 Hz. - Slices preincubated with 3H-dopamine were superfused with medium containing nomifensine 1 mumol/l. The overflow of tritium elicited by single pulses was 0.39% of the tritium content of the tissue. The overflow elicited by 4 pulses/1 Hz was 1.3-fold and the overflow elicited by 4 pulses/100 Hz 1.4-fold higher. Domperidone 1-100 nmol/l and sulpiride 10-1000 nmol/l increased up to 2.4-fold the overflow evoked by 4 pulses/1 Hz but increased only slightly the overflow evoked by single pulses or 4 pulses/100 Hz. - Slices preincubated with 3H-choline were superfused either with physostigmine-free medium or with medium containing physostigmine 1 mumol/l. In physostigmine-free medium, atropine did not increase the evoked overflow of tritium at any stimulation condition. In physostigmine-containing medium, the overflow elicited by single pulses was 0.18% of the tritium content of the tissue. The overflow elicited by 8 pulses/1 Hz was 2.0-fold and the overflow elicited by 8 pulses/100 Hz 2.2-fold higher. Atropine 2-200 nmol/l increased up to 2.4-fold the overflow evoked by 8 pulses/1 Hz but increased only slightly the overflow evoked by single pulses or 8 pulses/100 Hz. In physostigmine-free medium, sulpiride 10-1000 nmol/l did not change the single-pulse-evoked overflow of tritium in the absence but increased it in the presence of nomifensine 1 mumol/l. Single pulses elicit a large release of 3H-noradrenaline, 3H-dopamine and 3H-acetylcholine under the conditions of these experiments. Release elicited by single pulses is not subject to autoinhibition except for a small inhibition by spontaneously released transmitter in the case of dopaminergic and cholinergic axons.(ABSTRACT TRUNCATED AT 400 WORDS)
为了研究递质释放模式以及递质释放的自身抑制作用,用单个电脉冲或1Hz或100Hz的4个或8个脉冲串对兔脑切片进行场刺激。切片预先用3H-去甲肾上腺素(皮质)、3H-多巴胺(尾状核)或3H-胆碱(尾状核)孵育。预先用3H-去甲肾上腺素孵育的切片用含有1μmol/L地昔帕明的培养基进行灌流。单个脉冲引起的氚溢出量相当于组织中氚含量的0.19%。1Hz的4个脉冲引起的溢出量相似,而100Hz的4个脉冲引起的溢出量高5.1倍。10 - 1000nmol/L的育亨宾使1Hz的4个脉冲引起的溢出量增加达2.5倍,但不改变单个脉冲或100Hz的4个脉冲引起的溢出量。 - 预先用3H-多巴胺孵育的切片用含有1μmol/L诺米芬辛的培养基进行灌流。单个脉冲引起的氚溢出量为组织中氚含量的0.39%。1Hz的4个脉冲引起的溢出量高1.3倍,100Hz的4个脉冲引起的溢出量高1.4倍。1 - 100nmol/L的多潘立酮和10 - 1000nmol/L的舒必利使1Hz的4个脉冲引起的溢出量增加达2.4倍,但仅轻微增加单个脉冲或100Hz的4个脉冲引起的溢出量。 - 预先用3H-胆碱孵育的切片用不含毒扁豆碱的培养基或含有1μmol/L毒扁豆碱的培养基进行灌流。在不含毒扁豆碱的培养基中,阿托品在任何刺激条件下均不增加诱发的氚溢出量。在含有毒扁豆碱的培养基中,单个脉冲引起的溢出量为组织中氚含量的0.18%。1Hz的8个脉冲引起的溢出量高2.0倍,100Hz的8个脉冲引起的溢出量高2.2倍。2 - 200nmol/L的阿托品使1Hz的8个脉冲引起的溢出量增加达2.4倍,但仅轻微增加单个脉冲或100Hz的8个脉冲引起的溢出量。在不含毒扁豆碱的培养基中,10 - 1000nmol/L的舒必利在不存在诺米芬辛时不改变单个脉冲诱发的氚溢出量,但在存在1μmol/L诺米芬辛时增加该溢出量。在这些实验条件下,单个脉冲可引起大量3H-去甲肾上腺素、3H-多巴胺和3H-乙酰胆碱的释放。除了多巴胺能和胆碱能轴突中自发释放的递质有轻微抑制作用外,单个脉冲引起的释放不受自身抑制。(摘要截选至400字)