Comparison of results obtained with different methods for estimating GABA turnover in rat neostriatum.
Different methods for measuring GABA turnover in rat brain were compared. One method was based on the irreversible inhibition of GABA transaminase (EC 2.6.1.19) by microinjection of gamma-vinyl-GABA into neostriatum of rat. The accumulation of GABA was almost linear for 4 hr. The GABA turnover in control animals was estimated to be 25.8 +/- 1.1 nmole/mg protein/hr. Another method was based on the post mortal increase in GABA level in an 8 min interval after decapitation. This method gave a GABA turnover of 54.3 +/- 4.8 nmole/mg protein/hr in neostriatum. The methods were compared with respect to their ability to detect the effect of high doses of diazepam and morphine on the turnover rate of GABA. The GABA transaminase inhibition method resulted in a 27% and a 17% decrease in GABA turnover for diazepam and morphine respectively. The post mortem method did not detect any change in GABA turnover after administration of these drugs. Hypoglycemia leads to a decrease in GABA turnover of 17% with the GABA transaminase inhibition method and a 43% decrease in GABA turnover with the post mortem method. The advantages and limitations of the methods for estimating GABA turnover changes during drug exposure is discussed, and are compared with results from a third method based on steady state kinetics extracted from the literature.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008722:Methods; D009020:Morphine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007328:Insulin; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D000612:4-Aminobutyrate Transaminase; D003975:Diazepam