Modulation by nitric oxide of rat brain GABAA receptors.
The effect of nitric oxide (NO) on the function of GABAA receptors was studied in two different rat brain neuron populations. Cerebral cortex neuronal GABAA receptors were studied by preparing microsacs and evaluating 36Cl- accumulation. Whether nitric oxide was provided by sodium nitroprusside (SNP) or by the metabolic precursor precursor arginine there was a 15-25% reduction in the Vmax for GABA-stimulated 36Cl- accumulation. The arginine effect could be reversed by the NO synthase (NOS) inhibitor N omega-nitro-L-arginine. GABAA receptor mediated Cl- currents were studied in rat cerebellar granule cells by whole-cell patch clamp. S-Nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside and L-arginine reduced the Cl- current elicited by 10 microM GABA. The L-arginine effect was reversible upon its washing out. This circumstance indicates that NO produced by endogenous NOS can inhibit GABAA receptor function in cerebellar granule cells.
Zarri
I
I
Centro di Neurofisiologia Cerebrale, CNR, Genova, Italy.
Bucossi
G
G
Cupello
A
A
Rapallino
M V
MV
Robello
M
M
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002525:Cerebellar Cortex / Q000166:cytology*; D002540:Cerebral Cortex / Q000166:cytology*; D018118:Chloride Channels / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D015536:Down-Regulation; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D026423:S-Nitroso-N-Acetylpenicillamine; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010396:Penicillamine