Initial serotonin transport into viable platelets and imipramine binding to platelet membranes.
Transport of serotonin into human platelets is a paradigm for neuronal reuptake to investigate putatively low neurotransmitter availability in certain psychiatric diseases. However, inconsistent results have been obtained on serotonin binding to platelet membranes at equilibrium and transport during initial phase into isolated platelets. In the present study we applied a rapid oil-centrifugation technique to study (14)C-serotonin transport for 15s into viable human platelets during the initial phase, compared to the binding of (3)H-imipramine at equilibrium (60 min) to membranes isolated from platelets of the same individuals and to their blood serotonin levels. Platelets were viable for two h after the isolation procedure; concomitant with the decrease in viability transport also decreased. Initial transport into viable cells was observed for two min. Across 19 healthy individuals blood serotonin levels correlated with the halfmaximal saturation constants of binding, K(D), for imipramine but not with any other transport or binding parameters, such as V(max) or B(max). Inhibition studies with psychoactive drugs showed good correlation between transport during the initial phase and binding at equilibrium (r = 0.83). It is speculated that changes in the V(max) of transport reflect problems with isolation, pretreatment with drugs, the energy load of the cell, and polymorphism of the serotonin transporter. The latter shows a polymorphism in the 5'regulatory region with a 44-bp insertion (l, long form) or deletion (s, short form). Results by Greenberg et al. indicate that in platelets from healthy men the l-variant was associated with increased initial serotonin uptake. Thus for genotyping, we suggest to subdivide patient and control groups in addition to psychopathology also according to their peripheral biochemical lesions.
Rao
M L
ML
Department of Psychiatry and Psychotherapy, University of Bonn, Federal Republic of Germany. m.l.rao@uni-bonn.de
Frahnert
C
C
Zagorski
O
O
D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D005260:Female; D006801:Humans; D007099:Imipramine / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009994:Osmolar Concentration; D010976:Platelet Count; D011619:Psychotropic Drugs / Q000494:pharmacology; D012701:Serotonin / Q000097:blood*; D013696:Temperature; D013997:Time Factors
D011619:Psychotropic Drugs; D012701:Serotonin; D007099:Imipramine