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Lesioning of serotoninergic and noradrenergic nerve fibres of the rat brain does not decrease binding of 3H-clonidine and 3H-rauwolscine to cortical membranes

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Summary

α2-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 α2-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 ijections 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 (K D about 5 nmol/l; B max 217–247 fmoles/mg protein), whereas 3H-clonidine bound to a high affinity site (K D 0.6–1.4 nmol/l) and a low affinity site (K D 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 affintiy 3H-clonidine binding sites without reducing the number of high plus low affinity binding sites, indicating a denervation supersensitivity. K D- as well as B max-values for 3H-rauwolscine remained unaltered after 6-OH-DA-treatment. Since an increase in postsynaptic α2-adrenoceptors due to 6-OH-DA-administration might have masked a loss of presynaptic α2-adrenergic binding sites, rats were chronically treated with high doses of clonidine in order to prevent a possible supersensitivity of postsynaptic receptors. Even under these conditions 6-OH-DA did not reduce the number of 3H-clonidine and 3H-rauwolscine binding sites.

Injection of 5,7-DHT had no influence on binding parameters of 3H-clonidine and 3H-rauwolscine.

It is concluded that in the cerebral cortex the number of postsynaptic α2-adrenoceptors is much greater than that of presynaptic α2-adrenoceptors. Therefore, the changes in the number of presynaptic α2-adrenoceptors due to destruction of noradrenergic or/and serotoninergic neurons cannot be detected by equilibrium binding studies with 3H-clonidine or 3H-rauwolscine.

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Authors and Affiliations

  1. Pharmakologisches Institut, Universitätsklinikum Essen, Hufelandstrasse 55, D-4300, Essen, Federal Republic of Germany

    G. Groß, M. Göthert, U. Glapa & H.-J. Schümann

  2. Preclinical Research, Sandoz Ltd., CH-4002, Basel, Switzerland

    G. Engel

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  1. G. Groß
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  2. M. Göthert
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  3. U. Glapa
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  4. G. Engel
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  5. H.-J. Schümann
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Groß, G., Göthert, M., Glapa, U. et al. Lesioning of serotoninergic and noradrenergic nerve fibres of the rat brain does not decrease binding of 3H-clonidine and 3H-rauwolscine to cortical membranes. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 229–235 (1985). https://doi.org/10.1007/BF00515546

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  • DOI: https://doi.org/10.1007/BF00515546

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