Tuomisto J, Komulainen H
Acta Pharmacol Toxicol (Copenh). 1983 Sep;53(3):193-9. doi: 10.1111/j.1600-0773.1983.tb01124.x.
Effects of various concentrations of extracellular Ca on the high affinity uptake of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) as well as the effects of Ca on Cu-induced uptake inhibition were studied by using striatal, cortical and hypothalamic synaptosomes, respectively. The spontaneous release of all three amines from preloaded synaptosomes by Cu increased slightly with increasing external Ca up to 2.5 mM. The sensitivity to Ca of the accumulation of the amines into synaptosomes decreased in the order of DA greater than NA greater than 5-HT. Below 0.3 mM Ca, DA uptake increased due to concurrent decreased release of DA from synaptosomes. The pattern was similar but less evident for NA while 5-HT uptake and its spontaneous release did not change upon buffer Ca at all. The uptake inhibition of none of the amines depended on extracellular Ca. Zn reversed the Cu-induced inhibition of 5-HT uptake but increased additively the inhibition of DA uptake and that of NA uptake in vitro. The potency of Cu to inhibit uptake decreased when the protein concentration in the incubation medium was increased. Cysteine, added concurrently with Cu, did not protect uptake from the toxic influence of Cu. The results so far suggest that the primary mechanism in the Cu-induced inhibition of uptake is blocking the membrane uptake carrier. The release of an accumulated amine from synaptosomes may rather be secondary and result from the inhibition of the reuptake.
分别使用纹状体、皮质和下丘脑突触体，研究了不同浓度的细胞外钙对多巴胺（DA）、去甲肾上腺素（NA）和5-羟色胺（5-HT）高亲和力摄取的影响，以及钙对铜诱导的摄取抑制的影响。随着外部钙浓度增加至2.5 mM，铜从预加载的突触体中诱导释放的所有三种胺类的自发释放略有增加。胺类积累到突触体中对钙的敏感性按DA＞NA＞5-HT的顺序降低。在钙浓度低于0.3 mM时，由于突触体中DA释放同时减少，DA摄取增加。NA的情况类似但不太明显，而5-HT摄取及其自发释放根本不会因缓冲液中的钙而改变。所有胺类的摄取抑制均不依赖于细胞外钙。锌可逆转铜诱导的5-HT摄取抑制，但在体外可加性增加对DA摄取和NA摄取的抑制。当孵育培养基中的蛋白质浓度增加时，铜抑制摄取的效力降低。与铜同时添加的半胱氨酸不能保护摄取免受铜的毒性影响。目前的结果表明，铜诱导摄取抑制的主要机制是阻断膜摄取载体。从突触体中释放积累的胺类可能是次要的，是由再摄取抑制导致的。
