Enhancement of endogenous GABA release from rat synaptosomal preparations is mediated by alpha 2-adrenoceptors pharmacologically different from alpha 2-autoreceptors.
The effects of various adrenergic agents on the release of endogenous gamma-aminobutyric acid (GABA) and of [3H]GABA were studied in superfused synaptosomal preparations from rat hippocampus. Noradrenaline (NA) enhanced in a concentration-dependent way the release of endogenous GABA but did not affect the release of the radioactive amino acid. The effect of NA was mimicked by the alpha 2-adrenoceptor agonist, clonidine, but not by the alpha 1-agonist, phenylephrine. Accordingly, NA was antagonized by the alpha 2-adrenoceptor antagonist, yohimbine, but not by the alpha 1-antagonist, prazosin. Both (+)-mianserin and (-)-mianserin, used as alpha 2-adrenoceptor blockers, counteracted the NA-evoked release of endogenous GABA. The results suggest that GABA released from hippocampus crude synaptosomes is modulated by alpha 2-adrenoceptors pharmacologically different from the alpha 2-autoreceptors that modulate NA release and previously found to be blocked by (+)-mianserin but not by the (-) enantiomer (Raiteri et al., 1983).
Maura
G
G
Istituto di Farmacologia e Farmacognosia, Università di Genova, Italy.
Pittaluga
A
A
Ulivi
M
M
Raiteri
M
M
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D008803:Mianserin; D015016:Yohimbine; D005680:gamma-Aminobutyric Acid; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin