Ae. Santos et al., REGULATION OF INTRACELLULAR [CA2+] AND GABA RELEASE BY PRESYNAPTIC GABA(B) RECEPTORS IN RAT CEREBROCORTICAL SYNAPTOSOMES, Neurochemistry international, 27(4-5), 1995, pp. 397-406
In this study we determined the changes in the intracellular free Ca2 concentration, associated with the inhibitory modulation of the exocy
totic release of GABA by GABA(B) receptor activation in rat cerebrocor
tical synaptosomes. We observed that SK&F 97541 and (-)baclofen both a
ct as agonists of the presynaptic GABA(B) receptors in modulating GABA
release and Ca2+ influx due to KCl (10 mM) depolarization, but SK&F 9
7541 is more potent than (-)baclofen in modulating both Ca2+ influx an
d GABA release. Thus, activation of GABA(B) receptors by either SK&F 9
7541 (10 mu M) or by (-)baclofen (100 mu M) caused about 18% inhibitio
n of the increase in [Ca2+], due to KCl depolarization, and inhibited
the [H-3]GABA release by about 30%. The pharmacological similarities o
f the GABA(B) receptor activation in producing inhibition of both calc
ium channel mediated influx of Ca2+ and transmitter release suggest th
at presynaptic inhibition of GABA release by GABA(B) receptor activati
on may result, at least in part, from inhibition of Ca2+ influx throug
h P-type (or possibly Q-type) Ca2+ channels, sensitive to omega-Agatox
in IVA (200 nM). Furthermore, modulation of GABA release by GABA(B) re
ceptors was abolished by preincubation with pertussis toxin, suggestin
g that a pertussis toxin sensitive G protein may be the coupling facto
r between GABA(B) receptors and the voltage-dependent Ca2+ channels as
sociated with the exocytotic release of GABA in rat cerebrocortical ne
rve terminals.