Inhibition of neuronal uptake reduces the presynaptic effects of clonidine but not of alpha-methylnoradrenaline on the stimulation-evoked release of 3H-noradrenaline from rat occipital cortex slices.
The iminoimidazolidine clonidine reduced concentration-dependently the release of 3H-noradrenaline evoked by electrical stimulation from the rate cerebral cortex. Exposure to the neuronal uptake inhibitors cocaine (10 micro M), desipramine (0.1 to 1 micro M) and amphetamine (1 micro M) significantly increased the stimulation-evoked overflow of tritium. These uptake inhibitors antagonized the effects of clonidine on stimulation evoked 3H-noradrenaline release but failed to modify the inhibition induced by the catecholamine alpha-methylnoradrenaline. Inhibition of monoamine oxidase by preincubation of cerebral cortex slices with 0.5 mM pargyline significantly increased the stimulation-evoked overflow of tritium, but clonidine was as effective as in the controls in inhibiting 3H-noradrenaline overflow. The antagonism by desipramine of the clonidine-induced inhibition of neurotransmission could not be attributed to a blockade of presynaptic alpha-adrenoceptors because: (1) the facilitating effect of phentolamine on 3H-noradrenaline overflow was not modified in the presence of desipramine; (2) the magnitude of the inhibition of the stimulation-evoked 3H-noradrenaline release elicited by alpha-methylnoradrenaline was the same in the presence of cocaine or desipramine; (3) exposure to desipramine in the presence of cocaine did not further increase the stimulation-evoked release of 3H-transmitter. Since the catecholamine alpha-methylnoradrenaline inhibited neurotransmission in the presence of desipramine or cocaine, we can conclude that inhibition of neuronal uptake of noradrenaline antagonized selectively the presynaptic inhibitory effects of imidazolines on alpha 2-adrenoceptors. The influence of the inhibition of neuronal uptake on the presynaptic effects of imidazolines and catecholamines should be taken into account when the relative order of potencies of various alpha 2-adrenoceptors agonists is determined.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008771:Nordefrin / Q000494:pharmacology*; D009638:Norepinephrine / Q000031:analogs & derivatives* / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D014316:Tritium
D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D010293:Pargyline; D000661:Amphetamine; D003042:Cocaine; D003000:Clonidine; D008771:Nordefrin; D003891:Desipramine; D009638:Norepinephrine; D010646:Phentolamine