Catania M V, Sortino M A, Rampello L, Canonico P L, Nicoletti F
Institute of Pharmacology, University of Catania, School of Medicine, Italy.
Neuropharmacology. 1991 Feb;30(2):153-9. doi: 10.1016/0028-3908(91)90198-k.
Addition of adenosine deaminase to cultured cerebellar neurones, led to large increases in the influx of 45Ca2+ and hydrolysis of polyphosphoinositide. These effects were inhibited or attenuated by glutamate receptor antagonists (AP5 or MK-801) and were not observed in cells stimulated by maximum concentrations of glutamate or quisqualate. Stimulation of the influx of 45Ca2+ and hydrolysis of phosphoinositide by adenosine deaminase may be secondary to an enhanced release of endogenous glutamate that in turn activates specific excitatory amino acid receptors. Accordingly, adenosine deaminase potently increased release of D-[3H]aspartate, an effect that requires the presence of extracellular Na+ and is insensitive to inhibition by MK-801. None of the effects of adenosine deaminase may be simply related to a fall in endogenous adenosine. In fact, the action of adenosine deaminase was neither reversed by agonists (L-PIA or NECA), nor mimicked by antagonists (IBMX or theophylline) of adenosine receptors. It is speculated that adenosine deaminase stimulates release of neurotransmitter through a mechanism independent of depletion of adenosine. A possible direct action of adenosine deaminase should be taken into account when the enzyme is used to unmask the effects of endogenous adenosine.
向培养的小脑神经元中添加腺苷脱氨酶，会导致45Ca2+内流和多磷酸肌醇水解大幅增加。这些效应被谷氨酸受体拮抗剂（AP5或MK-801）抑制或减弱，并且在受到最大浓度谷氨酸或quisqualate刺激的细胞中未观察到。腺苷脱氨酶对45Ca2+内流和磷酸肌醇水解的刺激作用可能继发于内源性谷氨酸释放增强，进而激活特定的兴奋性氨基酸受体。因此，腺苷脱氨酶有力地增加了D-[3H]天冬氨酸的释放，这一效应需要细胞外Na+的存在，并且对MK-801的抑制不敏感。腺苷脱氨酶的这些效应可能与内源性腺苷的减少没有直接关系。事实上，腺苷脱氨酶的作用既不能被腺苷受体激动剂（L-PIA或NECA）逆转，也不能被腺苷受体拮抗剂（IBMX或茶碱）模拟。据推测，腺苷脱氨酶通过一种独立于腺苷耗竭的机制刺激神经递质释放。当使用该酶来揭示内源性腺苷的作用时，应考虑腺苷脱氨酶可能的直接作用。
