title: Is there a functional linkage between neurotransmitter uptake mechanisms and presynaptic receptors?
abstract: The possibility of interaction between neurotransmitter uptake mechanisms and presynaptic receptors regulating transmitter release was investigated using rat brain synaptosomes in superfusion. Various conditions were considered including: absence of substrate for the uptake with uptake potentially operative; absence of substrate and presence of uptake inhibitors; and uptake activated by added substrate, with or without uptake inhibitors. The release of [3H]-5-hydroxytryptamine ([3H]-5-HT) evoked by 15 mM KCl from cerebral cortex synaptosomes was inhibited by lysergic acid diethylamide. The 5-HT uptake inhibitors citalopram and chlorimipramine did not affect the inhibitory action of lysergic acid diethylamide. Clonidine decreased both the K+-evoked release of [3H]norepinephrine and that of [3H]-5-HT in cortical synaptosomes through the activation of presynaptic alpha-2 adrenoceptors. In superfusion conditions, the action of clonidine on [3H]norepinephrine release was not antagonized by the norepinephrine uptake inhibitors desipramine or cocaine; similarly, the inhibition of [3H]-5-HT release was unaffected when 5-HT uptake was blocked. The K+-evoked release of [3H]dopamine from striatal nerve terminals was potentiated by acetylcholine (ACh) through the activation of muscarinic presynaptic receptors. The action of ACh was not modified by the presence of nomifensine, a dopamine uptake inhibitor. Finally, in superfused cortical synaptosomes, the block of the high-affinity uptake of choline by hemicholinium-3 had no effect on the muscarinic autoreceptor-mediated inhibition of [3H]ACh release by ACh. Altogether the present results do not support the previously proposed idea that in nerve terminals a functional coupling may exist between uptake mechanisms and presynaptic receptors.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002997:Clomipramine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006426:Hemicholinium 3 / Q000494:pharmacology; D066298:In Vitro Techniques; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D014179:Neurotransmitter Uptake Inhibitors; D017981:Receptors, Neurotransmitter; D009627:Nomifensine; D006426:Hemicholinium 3; D012701:Serotonin; D011189:Potassium Chloride; D008238:Lysergic Acid Diethylamide; D003042:Cocaine; D003000:Clonidine; D000109:Acetylcholine; D002997:Clomipramine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine