Antagonist inhibition of GABAA-mediated chloride uptake is atypical in nigrocollicular areas.
Marked regional differences in the mRNA levels for the different subunits of the GABAA receptor may result in functional differences throughout the brain. The effects of different GABAA agonists and antagonists on GABAA receptor function was measured using 36Cl- uptake in microsacs made from cerebellum (CB), superior colliculus (SC), substantia nigra (SN), inferior colliculus (IC) or cortex (CT) containing equal amounts of protein. GABA increased Cl- uptake in all regions in a dose-dependent and saturable manner but with markedly different efficacies across brain regions. Maximal GABA-stimulated uptake was 59 +/- 2 nmoles of Cl- per mg protein in CT, 25 +/- 5 in SC, 24 +/- 4 in CB, 16 +/- 1 in IC and 6.7 +/- 1.4 in SN. Muscimol increased Cl- uptake with greater potency than GABA but with similar efficacies in CT, CB, SC and SN; the efficacy of muscimol in IC was increased to 27.4 +/- 5. Picrotoxin inhibited maximal GABA-stimulated Cl- uptake in CB, SC and CT but did not decrease uptake in IC or SN. Bicuculline methiodide completely inhibited uptake in CB and CT, partially inhibited uptake in IC, and did not affect uptake in SC and SN. These data provide functional support for regional heterogeneity of the GABAA receptor/Cl- ionophore between nigrocollicular regions and CB and CT.
Dept. Pharmacodynamics, University of Florida Health Sciences Center, Gainesville 32610.
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D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002712:Chlorides / Q000493:pharmacokinetics*; D002713:Chlorine; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D007245:Inferior Colliculi / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007476:Ionophores / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology; D013268:Stimulation, Chemical; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D013477:Superior Colliculi / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001640:Bicuculline; D002712:Chlorides; D002713:Chlorine; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D007476:Ionophores; D010852:Picrotoxin; D011868:Radioisotopes; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid