Transmitter release by non-receptor activation of the alpha-subunit of guanine nucleotide regulatory protein in rat striatal slices.
The effects of 5 mM NaF + 10 microM AlCl3, a direct activator of guanine nucleotide-binding proteins (G proteins), on the release of [3H]dopamine ([3H]DA), [3H]gamma-aminobutyric acid ([3H]GABA), and [3H]acethylcholine ([3H]ACh) were investigated in slices of rat striatum. When the tissue was exposed to NaF + AlCl3 the release of [3H]DA, [3H]GABA, and [3H]ACh was enhanced significantly. In a calcium-free solution the release of [3H]GABA and [3H]DA was increased by NaF+AlCl3 much more than in the presence of [Ca2+]o. In slice preparations taken from reserpinized animals, in which the vesicular storage of [3H]DA was therefore prevented, NaF + AlCl3 had no effect on [3H]DA release. HPLC analysis of the radioactivity of the perfusate showed that, in the presence of NaF + AlCl3, the content of dihydroxyphenylacetic acid (DOPAC) in perfusate samples increased significantly, while in pargyline-treated animals only the DA content was increased. Inhibition of DA carriers by nomifensine or low temperature prevented the effect of NaF + AlCl3. N-ethylmaleimide (NEM) preincubation did not modify the effect of NaF + AlCl3 on [3H]DA release Neomycin (0.1 mM), a phospholipase C (PLC) inhibitor, significantly decreased the effect of NaF + AlCl3 on [3H]DA and [3H]GABA release. The internal concentration of Ca2+ in synaptosomes was enhanced by NaF + AlCl3 in normal solution. However, [Ca2+]i was not influenced by NaF + AlCl3 in Ca(2+)-free medium. It is concluded that a non-receptor-mediated activation, by NaF + AlCl3, of the alpha-subunit of a G protein, results in a [Ca2+]o-independent release of DA and GABA, but not that of ACh.
Zelles
T
T
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Chernaeva
L
L
Baranyi
M
M
Déri
Z
Z
Adam-Vizi
V
V
Vizi
E S
ES
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D012969:Sodium Fluoride / Q000494:pharmacology; D013268:Stimulation, Chemical; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D017607:Aluminum Compounds; D002712:Chlorides; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D012430:Ruthenium Red; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D005576:Colforsin; D009627:Nomifensine; D000077410:Aluminum Chloride; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D012110:Reserpine; D012969:Sodium Fluoride; D010293:Pargyline; D010727:Phosphoric Diester Hydrolases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D009355:Neomycin; D000109:Acetylcholine; D005033:Ethylmaleimide; D002118:Calcium; D004298:Dopamine