Uptake, release, and modulation of release of noradrenaline in rabbit superior colliculus.
The noradrenaline content, the uptake of [3H]noradrenaline, and the release of previously incorporated [3H]noradrenaline were studied in slices of rabbit superior colliculus. The concentration of endogenous noradrenaline was higher in superficial than in deep layers of the superior colliculus. Upon incubation with [3H]noradrenaline, tritium was accumulated by a mechanism that was strongly inhibited by oxaprotiline but little inhibited by 6-nitroquipazine. Electrical stimulation at 0.2 or 3 Hz increased the outflow of tritium from slices preincubated with [3H]noradrenaline; the increase was almost abolished by tetrodotoxin or a low calcium medium. Clonidine reduced the evoked overflow of tritium, whereas yohimbine increased it and antagonized clonidine. The evoked overflow was also reduced by the dopamine D2-receptor-selective agonists apomorphine and quinpirole, an effect antagonized by sulpiride. The preferential opioid kappa-receptor agonist ethylketocyclazocine produced an inhibition that was counteracted by naloxone. Nicotine accelerated the basal outflow of tritium; part of the acceleration was blocked by hexamethonium. The muscarinic agonist oxotremorine slightly diminished the electrically evoked overflow, and its effect was abolished by atropine. The oxaprotiline-sensitive uptake of [3H]noradrenaline as well as the tetrodotoxin-sensitive and calcium-dependent overflow of tritium upon electrical stimulation (presumably reflecting the release of [3H]noradrenaline) indicate that noradrenaline is a neurotransmitter in the superior colliculus. The release of [3H]noradrenaline is modulated through alpha 2-adrenoceptors as well as dopamine D2-receptors, opioid kappa-receptors and nicotine and muscarine receptors. No clear evidence was found for modulation through beta-adrenoceptors, D1-receptors, serotonin receptors, opioid mu- or delta-receptors or receptors for GABA or glutamate. Only the alpha 2-adrenoceptors receive an endogenous agonist input, at least under the conditions of these experiments. The pattern of presynaptic modulation resembles that found for noradrenaline release in other rabbit brain regions, suggesting that all noradrenergic axons arising in the locus coeruleus possess similar presynaptic receptor systems.
Wichmann
T
T
Pharmakologisches Institut der Universität, Freiburg i.Br., F.R.G.
Starke
K
K
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000493:pharmacokinetics*; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000493:pharmacokinetics; D013477:Superior Colliculi / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D008376:Maprotiline; D012701:Serotonin; C027299:hydroxymaprotilin; D013779:Tetrodotoxin; D003000:Clonidine; D009638:Norepinephrine