TRANSMITTER RELEASE BY NONRECEPTOR ACTIVATION OF THE ALPHA-SUBUNIT OFGUANINE-NUCLEOTIDE REGULATORY PROTEIN IN RAT STRIATAL SLICES

The effects of 5 mM NaF + 10 mu M AlCl3, a direct activator of guanine nucleotide-binding proteins (G proteins), on the release of [H-3]dopa mine ([H-3]DA), [H-3]gamma-aminobutyric acid ([H-3]GABA), and [H-3]ace thylcholine ([H-3]ACh) were investigated in slices of rat striatum, Wh en the tissue was exposed to NaF + AlCl3 the release of [H-3]DA, [H-3] GABA, and [H-3]ACh was enhanced significantly, In a calcium-free solut ion the release of [H-3]GABA and [H-3]DA was increased by NaF + AlCl3, much more than in the presence of [Ca2+](o), In slice preparations ta ken from reserpinized animals, in which the vesicular storage of [H-3] DA was therefore prevented, NaF + AlCl3 had no effect on [H-3]DA relea se, HPLC analysis of the radioactivity of the perfusate showed that, i n the presence of NaF + AlCl3, the content of dihydroxyphenylacetic ac id (DOPAC) in perfusate samples increased significantly, while in parg yline-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 [H-3]DA release, Neomycin (0.1 mM), a phospho lipase C (PLC) inhibitor, significantly decreased the effect of NaF AlCl3 on [H-3]DA and [H-3]GABA release. The internal concentration of Ca2+ in synaptosomes was enhanced by NaF + AlCl3 in normal solution, H owever, [Ca2+](i) was not influenced by NaF + AlCl3 in Ca2+-free mediu m. It is concluded that a non-receptor-mediated activation, by NaF + A lCl3, of the alpha-subunit of a G protein, results in a [Ca2+](o)-inde pendent release of DA and GABA, but not that of ACh. (C) 1995 Wiley-Li ss.