Modulation of serotonin uptake kinetics by ions and ion gradients in human placental brush-border membrane vesicles.
Modulation of serotonin uptake kinetics by ions and ion gradients in human placental brush-border membrane vesicles.
复制标题
人胎盘刷状缘膜囊泡中离子和离子梯度对血清素摄取动力学的调节。
DOI：
10.1021/bi00459a022
复制
发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Ganapathy,V
中科院分区：
文献类型：
--
作者：
Cool,DR;Leibach,FH;Ganapathy,V
乔治亚州奥古斯塔医学院细胞和分子生物学教研室1989年8月31日收到修订稿，1989年10月24日收到摘要：研究了Na+、Cl“、H+和K+对正常足月胎盘刷状缘膜囊膜5-羟色胺摄取动力学的调节。在两种情况下，5-羟色胺的初始摄取速率都是离子浓度的双曲线函数，表明一个5-羟色胺分子的转运涉及一个Na+和一个Cl“。Na+和Cl“的表观解离常数分别为145和79 mM，外加Na+增加了转运体的Fmax，也增加了转运体对5-羟色胺的亲和力，对Fmax和Kt也有相似的影响，但对Kt的影响小于Na+。有或没有跨膜pH梯度的内酸性pH的存在，刺激了对氯化钠依赖的5-羟色胺的摄取。体内[H+]对转运功能的影响是增加转运体对5-羟色胺的Fmax，降低转运体对5-羟色胺的亲和力。囊泡内K+的存在也极大地刺激了5-羟色胺摄取的初始速率，并且在pH 7.5时的刺激作用大于在pH 6.5时的刺激作用。在两个pH值下，这种刺激都是体内K+浓度的双曲线函数，表明一个5-羟色胺分子的每一个转运都涉及一个K+。PH 6.5时K+的表观解离常数为5.6 mM，pH 7.5时表观解离常数为4.0 mM。体内[K+]对摄取动力学的影响与体内[H+]相似。它增加了Fmax，但降低了对5-羟色胺转运体的亲和力。此外，内部[H+]对动力学参数的影响被囊泡内K+的存在所掩盖，这表明内部K+和内部H+之间存在竞争。
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912-2100 Received August 31, 1989; Revised Manuscript Received October 24, 1989 abstract: The modulation of serotonin uptake kinetics by Na+, Cl”, H+, and K+ was investigated in brush-border membrane vesicles prepared from normal humanterm placentas. The presence of Na+ and Cl" in the external medium was mandatory for the function of the serotonin transporter. In both cases, the initial uptake rate of serotonin was a hyperbolic function of the ion concentration, indicating involvement of one Na+ and one Cl" per transport of one serotonin molecule. The apparent dissociation constant for Na+ and Cl" was 145 and 79 mM, respectively. The external Na+ increased the Fmax of the transporter and also increased the affinity of the transporter for serotonin. The external Cl" also showed similar effects on the Fmax and the Kt, but its effect on the Kt was small compared to that of Na+. The presence of an inside-acidic pH, with or without a transmembrane pH gradient, stimulated the NaCl-dependent serotonin uptake. The effect of internal [H+] on the transport function was to increase the Fmax and decrease the affinity of the transporterfor serotonin. The presence of K+ inside the vesicles also greatly stimulated the initial rates of serotonin uptake, and the stimulation was greater at pH 7.5 than at pH 6.5. This stimulation was a hyperbolic function of the internal K+ concentration at both pH values, indicating involvement of one K+ per transport of one serotonin molecule. The apparent dissociation constant for K+ was 5.6 mM at pH 6.5 and 4.0 mM at pH 7.5. The effects of internal [K+] on the uptake kinetics were similar to those of internal [H+]. It increased the Fmax but decreased the affinity for the transporter for serotonin. In addition, the effects of internal [H+] on the kinetic parameters were masked by the presence of K+ inside the vesicles, indicating competition between internal K+ and internal H+.