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Pharmacologically distinct release modulating subtypes of the GABAB receptor population
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Pharmacological Research, Vol. 26, Supplement 1, 1992
PHARMACOLOGICALLYDISTINCT RELEASE MODULATING SUBTYPES OF THE GABA RECEPTORPOPULATION ' Giam I?attista Bonanno, Marco Lanza & Maurizio Raiteri Istituto di Farmacologia e Farmacognosia, Viale Cembrano 4, 16148 Genova (Italy). The GABAB receptors inhibiting endogenous GABA, glutamate (GLU) or somatostatin-like immunoreactivity (SRIF-LI) release have been studied in rat cerebrocortical synaptosomes in superfusion. The GABAB receptor agonist (-)baclofen inhibited the K+-evoked release of GABA (EC50: 1.1 + 0.1 PM), GLU (EC o: 1.5 ?r 0.1 PM) and SRIF-LI (EC50: 1.3 + 0.1 PM). On ? he contrary, the GABAA receptor agonist muscimol was inactive up to 100 PM. Exogenously added GABA also inhibited the K+-evoked release of GLU and SRIF-LI (EC5 : 2.8 + 0.3 PM and 1.8 + 0.2 and its effec t! was not counteracted by the PM, respectively) GABAA receptor antagonists bicuculline or picrotoxin. The receptor antagonist phaclofen reduced the inhibitory
35348) antagonized 10 PM (-)baclofen on GLU (IC o: 4.1 + 0.8 FM) and SRIF-LI (IC50: 3.6 5 0.7 PM) release bu ii not on GABA The results suggest the existence of three different release. in the rat cerebral cortex. subtypes of the GABAB receptor
A POSSIBLERELATIONSHIP BETWEEN TAURINE AND SYNAPTOGENESISIN THE DEVELOPING RAT BRAIN R. J. Huxtable and P.-L. Lleu Departmentof Pharmacology,College of Medicine, University of Arizona, Tucson, Arizona 85724, USA. Taurine is unique among the neuroactiveamino acids in that it attains the highest concentration in the brain in development,levels falling thereafter. Other amino acids show an oppositedevelopmentalpattern. In the brain synaptosomalP,B fraction, for example,taurine levels are 150 pal/g protein at day 7 of life, but only 30 ~01 taurine/gprotein on day 56. In inversecorrelation with the changein taurine, the synapticdensity, as measured by mg protein in the Pa fraction/g brain, increasesover this period. When pregnantrats are maintainedon drinking water containing 1% of the taurine-depleting agent,guanidinoethanesulfonate,theresulting pups havelowerbraintaurinelevels than those born to control rats. Guanidinoethanesulfonateexposurehas no effect on brain weight or body weight. However, in pups exposedto guanidinoethanesulfonate,synaptosomaldensity is increasedat all the time points examined(7, 21, 28, and 56 days). These observationsraise a possibility thattaurine, a neuroinhibitory amino acid,may be one of the factors regulating synaptogenesis.
Pharmacological Research, Vol. 26, Supplement 1, 1992
PHARMACOLOGICALLYDISTINCT RELEASE MODULATING SUBTYPES OF THE GABA RECEPTORPOPULATION ' Giam I?attista Bonanno, Marco Lanza & Maurizio Raiteri Istituto di Farmacologia e Farmacognosia, Viale Cembrano 4, 16148 Genova (Italy). The GABAB receptors inhibiting endogenous GABA, glutamate (GLU) or somatostatin-like immunoreactivity (SRIF-LI) release have been studied in rat cerebrocortical synaptosomes in superfusion. The GABAB receptor agonist (-)baclofen inhibited the K+-evoked release of GABA (EC50: 1.1 + 0.1 PM), GLU (EC o: 1.5 ?r 0.1 PM) and SRIF-LI (EC50: 1.3 + 0.1 PM). On ? he contrary, the GABAA receptor agonist muscimol was inactive up to 100 PM. Exogenously added GABA also inhibited the K+-evoked release of GLU and SRIF-LI (EC5 : 2.8 + 0.3 PM and 1.8 + 0.2 and its effec t! was not counteracted by the PM, respectively) GABAA receptor antagonists bicuculline or picrotoxin. The receptor antagonist phaclofen reduced the inhibitory
35348) antagonized 10 PM (-)baclofen on GLU (IC o: 4.1 + 0.8 FM) and SRIF-LI (IC50: 3.6 5 0.7 PM) release bu ii not on GABA The results suggest the existence of three different release. in the rat cerebral cortex. subtypes of the GABAB receptor
A POSSIBLERELATIONSHIP BETWEEN TAURINE AND SYNAPTOGENESISIN THE DEVELOPING RAT BRAIN R. J. Huxtable and P.-L. Lleu Departmentof Pharmacology,College of Medicine, University of Arizona, Tucson, Arizona 85724, USA. Taurine is unique among the neuroactiveamino acids in that it attains the highest concentration in the brain in development,levels falling thereafter. Other amino acids show an oppositedevelopmentalpattern. In the brain synaptosomalP,B fraction, for example,taurine levels are 150 pal/g protein at day 7 of life, but only 30 ~01 taurine/gprotein on day 56. In inversecorrelation with the changein taurine, the synapticdensity, as measured by mg protein in the Pa fraction/g brain, increasesover this period. When pregnantrats are maintainedon drinking water containing 1% of the taurine-depleting agent,guanidinoethanesulfonate,theresulting pups havelowerbraintaurinelevels than those born to control rats. Guanidinoethanesulfonateexposurehas no effect on brain weight or body weight. However, in pups exposedto guanidinoethanesulfonate,synaptosomaldensity is increasedat all the time points examined(7, 21, 28, and 56 days). These observationsraise a possibility thattaurine, a neuroinhibitory amino acid,may be one of the factors regulating synaptogenesis.