Lesioning of serotoninergic and noradrenergic nerve fibres of the rat brain does not decrease binding of 3H-clonidine and 3H-rauwolscine to cortical membranes.
alpha 2-Adrenoceptors located presynaptically on nerve terminals are known to modulate the release of neurotransmitters from noradrenergic and serotoninergic neurons. The pre- and/or postsynaptic localization of binding sites for alpha 2-adrenergic radioligands, the agonist 3H-clonidine and the antagonist 3H-rauwolscine, was investigated in the rat cerebral cortex by the use of specific neurotoxins. Intracerebroventricular injections of 6-hydroxydopamine (6-OH-DA) and 5,7-dihydroxytryptamine (5,7-DHT) were used to destroy the noradrenergic and serotoninergic neurons, respectively, and the success of the treatment was controlled by measurement of tritium accumulation in cortex slices incubated with 3H-noradrenaline or 3H-serotonin. In cortical membranes, 3H-rauwolscine bound to a single site (KD about 5 nmol/l; Bmax 217-247 fmoles/mg protein), whereas 3H-clonidine bound to a high affinity site (KD 0.6-1.4 nmol/l) and a low affinity site (KD 6-10 nmol/l). The total number of high plus low affinity 3H-clonidine binding sites was about two thirds of the number of 3H-rauwolscine binding sites. 6-OH-DA treatment significantly increased the number of high affinity 3H-clonidine binding sites without reducing the number of high plus low affinity binding sites, indicating a denervation supersensitivity. KD- as well as Bmax-values for 3H-rauwolscine remained unaltered after 6-OH-DA-treatment. Since an increase in postsynaptic alpha 2-adrenoceptors due to 6-OH-DA-administration might have masked a loss of presynaptic alpha 2-adrenergic binding sites, rats were chronically treated with high doses of clonidine in order to prevent a possible supersensitivity of postsynaptic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Gross
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Göthert
M
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Glapa
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U
Engel
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Schümann
H J
HJ
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003000:Clonidine / Q000378:metabolism*; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D011985:Receptors, Serotonin / Q000502:physiology*; D014316:Tritium; D015016:Yohimbine / Q000378:metabolism*
D006892:Hydroxydopamines; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D014316:Tritium; D015016:Yohimbine; D015116:5,7-Dihydroxytryptamine; D016627:Oxidopamine; D003000:Clonidine; D009638:Norepinephrine