title: Modulation of serotonin uptake kinetics by ions and ion gradients in human placental brush-border membrane vesicles.
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)
authors.affiliation: Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
authors.forename: D R
authors.initials: DR
authors.lastname: Cool
authors.forename: F H
authors.initials: FH
authors.lastname: Leibach
authors.forename: V
authors.initials: V
authors.lastname: Ganapathy
mesh_terms: D002712:Chlorides / Q000494:pharmacology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D010920:Placenta / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D012701:Serotonin / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D012701:Serotonin; D012964:Sodium; D011188:Potassium