The effects of GABAB receptor agonists and antagonists on potassium-stimulated [Ca2+]i in rat brain synaptosomes.
The effects of GABAB agonists and putative antagonists on intrasynaptosomal calcium ion concentrations ([Ca2+]i) after stimulation with potassium ions were studied with the fluorescent probe Quin 2. gamma-Aminobutyric acid and (-)-baclofen, but not (+)-baclofen, produced a dose-dependent inhibition of the potassium-stimulated [Ca2+]i in cortical synaptosomes from the rat. This effect was mimicked by another GABAB agonist SL75102 and weakly by muscimol. It was not inhibited by the alpha-adrenoceptor antagonist phentolamine. This system thus appears to provide a useful test of GABAB receptor function. None of the putative GABAB antagonists, phaclofen, delta-aminovaleric acid or beta-phenyl GABA inhibited responses to (-)-baclofen. Indeed, all three compounds produced similar responses to that seen with (-)-baclofen, suggesting that they act as agonists in this system. These data suggest that those GABAB receptors modulating [Ca2+]i have a distinct pharmacology from post-synaptic GABAB receptors, defined in electrophysiological experiments.
Stirling
J M
JM
Astra Neuroscience Research Unit, London, U.K.
Cross
A J
AJ
Robinson
T N
TN
Green
A R
AR
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D018756:GABA Antagonists; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018756:GABA Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D002118:Calcium