Characterization of the [3H]-desipramine binding site of the bovine adrenomedullary plasma membrane.
The specific (i.e. nisoxetine-sensitive) binding of [3H]desipramine was studied in membranes prepared from bovine adrenal medullae. (1) [3H]desipramine bound reversibly and with high affinity (KD = 2.8 nmol/l) to a single class of non-interacting binding sites (Hill coefficient = 0.96); the maximal number of binding sites (Bmax) was 2.1 pmol/mg protein. (2) Binding of [3H]desipramine was dependent on [Na+] and [Cl-]. Increasing the concentrations of these ions increased binding. (3) Substrates and inhibitors of the neuronal noradrenaline transport system (uptake1) inhibited binding of [3H]desipramine with a rank order of potency typical for an interaction with the uptake1 carrier. The characteristics of [3H]desipramine binding remained essentially unchanged after solubilization of adrenomedullary membranes with the non-ionic detergent digitonin. The results indicate that the plasma membrane of bovine adreno-medullary cells is endowed with the neuronal uptake1 transporter.
Michael-Hepp
J
J
Institut für Pharmakologie und Toxikologie, Universität Würzburg, FRG.
Blum
B
B
Bönisch
H
H
D000313:Adrenal Medulla / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002712:Chlorides / Q000494:pharmacology; D003891:Desipramine / Q000378:metabolism* / Q000493:pharmacokinetics; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D016716:PC12 Cells; D051381:Rats; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012964:Sodium / Q000494:pharmacology; D012995:Solubility; D027981:Symporters; D014316:Tritium
D002352:Carrier Proteins; D002712:Chlorides; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; C493226:Slc6a2 protein, rat; D027981:Symporters; C036079:desipramine receptor; D005473:Fluoxetine; D014316:Tritium; C011386:nisoxetine; D012964:Sodium; D003891:Desipramine; D009638:Norepinephrine