Contrasting effects of the GABA transaminase inhibitors gamma-vinylGABA and aminooxyacetic acid on arterial pressure following injection into nucleus tractus solitarius.
The effect of injection of inhibitors of GABA-transaminase into the nucleus tractus solitarius (NTS) on arterial pressure was examined in anesthetized rats. Two typical GABA-transaminase inhibitors, gamma-vinylGABA (GVG) and aminooxyacetic acid (AOAA), increased arterial pressure when injected into the NTS, a response similar to that elicited by direct stimulation of GABA receptors in the NTS. However, with neither drug was the response consistent with the action of inhibiting GABA-T. The response elicited by GVG, despite GVG acting as an irreversible inhibitor of GABA-T, could be reproduced with subsequent injections. Still, the pressor response to GVG could be reversed by blockade of GABAB-receptors with CGP-35348, suggesting that GVG injection did increase GABA-mediated neural transmission. In contrast, the pressor response to AOAA could not be antagonized by blockade of either GABAA or GABAB receptors. These results suggest that acute inhibition of GABA-T does not necessarily result in an increase in GABA-mediated neural transmission.
Tsukamoto
K
K
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Sved
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D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000614:Aminocaproates / Q000008:administration & dosage / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D007267:Injections; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020888:Vigabatrin
D000614:Aminocaproates; D000625:Aminooxyacetic Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin