Richardson I W, Szerb J C
Br J Pharmacol. 1974 Dec;52(4):499-507. doi: 10.1111/j.1476-5381.1974.tb09717.x.
1 In order to establish the origin of the increased efflux of radioactivity caused by electrical stimulation of cerebral cortical slices which had been incubated with [(3)H]-choline, labelled choline and acetylcholine (ACh) collected by superfusion were separated by gold precipitation.2 In the presence of physostigmine electrical stimulation (1 Hz, 10 min) increased the release of only [(3)H]-ACh which was greatly enhanced by the addition of atropine.3 Continuous stimulation in the presence of physostigmine resulted in an evoked release of [(3)H]-ACh which declined asymptotically. This evoked release appeared to follow first-order kinetics with a rate constant which remained stable over the course of prolonged stimulation.4 The rate constant for the evoked release of [(3)H]-ACh with 1 Hz stimulation was three times greater in the presence of physostigmine and atropine than in the presence of physostigmine alone, while the size of the store from which [(3)H]-ACh was released was nearly identical under these two conditions.5 In the absence of physostigmine and atropine, stimulation caused the appearance of only [(3)H]-choline in the samples.6 Reduction of [(3)H]-ACh stores before the application of physostigmine resulted in a reduced evoked release of total radioactivity, both in the absence or presence of physostigmine and atropine, and decreased the evoked release of [(3)H]-ACh without affecting the release of [(3)H]-choline.7 Results suggest that electrical stimulation of cortical slices which had been incubated with [(3)H]-choline causes the release of only [(3)H]-ACh, both in the presence or absence of an anticholinesterase. The evoked increase in the efflux of total radioactivity is therefore a good measure of the release of [(3)H]-ACh.
为了确定用[(3)H]-胆碱孵育的大脑皮层切片经电刺激后放射性流出增加的来源,通过金沉淀法分离了经超灌流收集的标记胆碱和乙酰胆碱(ACh)。
在毒扁豆碱存在的情况下,电刺激(1赫兹,10分钟)仅增加[(3)H]-ACh的释放,而加入阿托品后这种释放会大大增强。
在毒扁豆碱存在的情况下持续刺激导致[(3)H]-ACh的诱发释放,该释放呈渐近性下降。这种诱发释放似乎遵循一级动力学,其速率常数在长时间刺激过程中保持稳定。
在毒扁豆碱和阿托品存在的情况下,1赫兹刺激诱发[(3)H]-ACh释放的速率常数比仅存在毒扁豆碱时大三倍,而在这两种条件下[(3)H]-ACh释放的储存量大小几乎相同。
在不存在毒扁豆碱和阿托品的情况下,刺激仅使样品中出现[(3)H]-胆碱。
在应用毒扁豆碱之前减少[(3)H]-ACh储存量,无论是否存在毒扁豆碱和阿托品,都会导致总放射性的诱发释放减少,并减少[(3)H]-ACh的诱发释放,而不影响[(3)H]-胆碱的释放。
结果表明,用[(3)H]-胆碱孵育的皮层切片经电刺激后,无论是否存在抗胆碱酯酶,都只会释放[(3)H]-ACh。因此,诱发的总放射性流出增加是[(3)H]-ACh释放的良好指标。