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Naunyn Schmiedebergs Arch Pharmacol. 1986 Dec;334(4):403-11.

Binding of 3H-desipramine to the neuronal noradrenaline carrier of rat phaeochromocytoma cells (PC-12 cells).


The specific (i.e., nisoxetine-sensitive) binding of 3H-desipramine was studied in purified plasma membranes of PC-12 cells (rat phaeochromocytoma cells). 3H-desipramine bound reversibly and with high affinity (KD = 4.5 nmol/l) to a single, non-interacting site (Hill coefficient = 1.04); the maximal number of binding sites (Bmax) was 19.6 pmol/mg protein. Like the uptake of noradrenaline (by uptake1), the binding of 3H-desipramine was dependent on both sodium and chloride. The stimulation of binding by chloride and sodium was characterized by a Hill coefficient of about 1 and 2, respectively. Both, chloride and sodium, slowed the rate of dissociation of bound 3H-desipramine. Increasing concentrations of sodium decreased the KD of 3H-desipramine binding without altering the Bmax. The binding of 3H-desipramine was inhibited by tricyclic antidepressants and other noradrenaline uptake blockers. There was a highly significant correlation between the potencies of a series of drugs for the inhibition of 3H-desipramine binding and for the inhibition of 3H-noradrenaline uptake into intact PC-12 cells. Both, binding of 3H-desipramine and uptake of 3H-noradrenaline, were stereoselectively inhibited by the enantiomers of cocaine and oxaprotiline. However, for most of the substrates of uptake1 the IC50 for inhibition of 3H-desipramine binding was much higher than that for inhibition of 3H-noradrenaline uptake. Nevertheless, noradrenaline competitively inhibited 3H-desipramine binding and unmasked dissociation of bound 3H-desipramine. Thus, 3H-desipramine probably binds to the substrate recognition site.(ABSTRACT TRUNCATED AT 250 WORDS).

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