Modulation of serotonin uptake kinetics by ions and ion gradients in human placental brush-border membrane vesicles

Biochemistry. 1990 Feb 20;29(7):1818-22. doi: 10.1021/bi00459a022.

Abstract

The modulation of serotonin uptake kinetics by Na+, Cl-, H+, and K+ was investigated in brush-border membrane vesicles prepared from normal human term 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 Vmax of the transporter and also increased the affinity of the transporter for serotonin. The external Cl- also showed similar effects on the Vmax 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 Vmax and decrease the affinity of the transporter for 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+].(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chlorides / pharmacology
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Microvilli / drug effects
  • Microvilli / metabolism*
  • Osmolar Concentration
  • Placenta / metabolism*
  • Potassium / pharmacology
  • Pregnancy
  • Serotonin / metabolism*
  • Sodium / pharmacology*

Substances

  • Chlorides
  • Serotonin
  • Sodium
  • Potassium