Evidence against a functional link between noradrenaline uptake mechanisms and presynaptic alpha-2 adrenoceptors.
Slices prepared from rat cerebral cortex were labelled with 3H-noradrenaline and superfused. Electrical field stimulation was carried out 15 min (S1) and 45 min (S2) after the start of collection of 5-min samples using 4 pulses delivered at 100 Hz. Drugs acting at alpha 2-adrenoceptors were added 20 min before S2, and their effects were evaluated using the S2/S1-ratio. The alpha 2-adrenoceptor antagonists idazoxan (1 mumol/l) and rauwolscine (1 mumol/l) failed to increase stimulation-evoked overflow of radioactivity in the absence or presence of the noradrenaline reuptake inhibitor desipramine (1 mumol/l). This indicates that the duration of electrical stimulation was too short to allow development of alpha 2-adrenoceptor-mediated autoinhibition by released noradrenaline. The effect of clonidine (3-1000 nmol/l) on stimulation-evoked overflow of radioactivity was tested in the absence and presence of three different reuptake inhibitors (desipramine, 1 mumol/l; maprotiline, 1 mumol/l; cocaine, 10 mumol/l). The analysis yielded identical concentration-response curves under all conditions. These results argue against an action of inhibitors of neuronal reuptake of noradrenaline at the presynaptic alpha 2-adrenoceptor and against the concept of a functional link between uptake site and receptor.
Zier
G
G
Institute of Pharmacology, University of Vienna, Austria.
Drobny
H
H
Valenta
B
B
Singer
E A
EA
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine