Clonidine differentially modulates the release of endogenous GABA in various rat brain areas.
The effects of clonidine on the release of endogenous gamma-aminobutyric acid (GABA) have been studied in superfused synaptosomes prepared from rat hypothalamus, nucleus tractus solitarii (NTS) and cerebellum. Clonidine enhanced in a concentration-dependent manner the basal release of GABA from hypothalamus and NTS synaptosomes. In contrast, the imidazoline did not affect the release of the amino acid from the cerebellar preparation. The alpha 2-adrenoceptor antagonist yohimbine prevented the releasing effect of clonidine, while the alpha 1-adrenoceptor antagonist prazosin was ineffective. The results show that the release of GABA from hypothalamus or NTS nerve endings can be enhanced by clonidine through the activation of adrenoceptors of the alpha 2 subtype. The GABAergic nerve terminals of cerebellum do not seem to possess presynaptic adrenoceptors by which clonidine can regulate the basal outflow of the amino acid. The results suggest that some of the clonidine effects may occur through activation of the GABA system.
Pittaluga
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A
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Torelli
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R
Raiteri
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M
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007093:Imidazoles; D010656:Phenylephrine; D015016:Yohimbine; D005680:gamma-Aminobutyric Acid; D003000:Clonidine; D011224:Prazosin