[3H]desipramine labels with high affinity the neuronal transporter for adrenaline in the frog heart.
Desipramine, a tricyclic antidepressant, inhibits the neuronal uptake of adrenaline and noradrenaline and, as a radioligand, labels the noradrenaline transporter in central and peripheral tissues of the rat. To study whether [3H]desipramine also labels the neuronal adrenaline transporter in vitro, its binding was evaluated in the frog heart, a tissue with a rich adrenergic innervation but virtually devoid of noradrenergic innervation. [3H]Desipramine binding to membranes from the frog heart was of high affinity (Kd = 1.94 nM) and was potently inhibited by nisoxetine and (+)oxaprotiline. Unexpectedly, [3H]desipramine binding to the transporter for adrenaline in the frog heart was also sensitive to inhibition by imipramine and the atypical antidepressants mianserin and iprindol. This is the first study to demonstrate radioligand binding to the neuronal transporter for adrenaline. The results indicate that the pharmacological profile of the transporter for adrenaline may be different from that of the noradrenergic transporter, if species differences can be excluded. It remains to be established if the affinity of imipramine, mianserin and iprindol for the adrenaline transporter contributes to their therapeutic efficacy in depression.
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism; D003891:Desipramine / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011894:Rana pipiens; D051381:Rats; D011919:Rats, Inbred Strains
D002352:Carrier Proteins; D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine