Time course of effects of 3-mercaptopropionic acid on GABA levels in different brain regions in guinea pigs: possible relationship with associated cardiovascular changes.
In anesthetized guinea pigs, we examined heart rate, arterial pressure, and GABA levels in four brain regions after systemic administration of 3-mercaptopropionic acid, an inhibitor of GABA synthesis. After i.p. injection of 195 mg/kg, significant reductions in GABA were first noted at 15 minutes in the cerebellum (-39%), 30 minutes in the hypothalamus (-27%), 60 minutes in the medulla pons (-34%) and 90 minutes in the cerebral cortex (-43%). Cardiovascular function was unaltered at 15 minutes but heart rate and arterial pressure were both significantly elevated at 30 minutes. By 60 minutes, however, heart rate had fallen below control. Injection of a lower dose (97.5 mg/kg i.p.) of 3-MP produced significant increases in heart rate and arterial pressure in 4 of 11 guinea pigs tested. When GABA levels in the same four brain regions were examined at 90 minutes and compared to corresponding levels from vehicle-treated guinea pigs, significant reductions were seen only in the hypothalamus and only in those animals displaying tachycardia and pressor responses. These findings are consistent with our previous results indicating that decreased GABA levels in the hypothalamus and in the medulla pons are responsible for the increases and decreases in heart rate, respectively, seen after systemic administration of 3-mercaptopropionic acid.
Alsip
N L
NL
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202.
DiMicco
J A
JA
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D015097:3-Mercaptopropionic Acid