Muscarinic receptors mediating inhibition of gamma-aminobutyric acid release in rat corpus striatum and their pharmacological characterization.
The effects of acetylcholine (ACh) and of cholinergic agonists on the release of tritiated gamma-aminobutyric acid ([3H]GABA) were studied in superfused synaptosomes prepared from rat corpus striatum and prelabeled with the radioactive amino acid. ACh, oxotremorine or (-)-nicotine, all tested at 100 microM had no effect on the spontaneous outflow of [3H]GABA. The depolarization-evoked overflow obtained by exposing the synaptosomes to 9 mM KCl was decreased in a concentration-dependent manner by ACh, oxotremorine, oxotremorine-M or carbachol. The maximal inhibition caused by ACh was 50%. The EC50 (agonist concentration causing half-maximal effect) amounted to 1 microM. Oxotremorine and oxotremorine-M were almost equipotent to ACh, whereas the concentration-response curve of carbachol was slightly (although not significantly) shifted to the right with respect to that of ACh. (-)-Nicotine (100 microM) did not affect the K(+)-evoked [3H]GABA overflow. ACh also inhibited the K(+)-evoked release of endogenous GABA. The inhibitory effect of 10 microM ACh on the release of [3H]GABA evoked by 9 mM KCl was insensitive to the nicotinic antagonist mecamylamine (10 microM) but it was potently blocked by the muscarinic antagonist atropine (IC50 = 5 nM) and weakly antagonized by pirenzepine, dicyclomine and AF-DX 116. The pharmacological profile of this receptor was very similar to that of the muscarinic autoreceptors regulating [3H]ACh release. The extent of [3H]GABA release inhibition caused by ACh did not differ between dorsal and ventral striatum. The inhibitory effect of ACh was much less pronounced in hippocampus and cortex than in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
Raiteri
M
M
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Marchi
M
M
Paudice
P
P
Pittaluga
A
A
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011976:Receptors, Muscarinic; D005680:gamma-Aminobutyric Acid; D010095:Oxotremorine; D009538:Nicotine; D000109:Acetylcholine