Injection of L-allylglycine into the posterior hypothalamus in rats causes decreases in local GABA which correlate with increases in heart rate.
Injection of the GABA antagonist, bicuculline methiodide into the posterior hypothalamus of rats has been shown to cause marked increases in heart rate and lesser elevations in blood pressure. Allylglycine is a potent inhibitor of the synthetic enzyme for GABA, glutamic acid decarboxylase, only after in vivo biotransformation into its active form, 2-keto-4-pentenoic acid, through a stereospecific amino acid oxidase. The posterior hypothalamus is thought to contain substantial activity only of L-amino acid oxidase. In this study, the stereoisomers of allylglycine were injected into the posterior hypothalamus at a site also shown to be reactive to bicuculline. Injection of L-allylglycine but not D-allylglycine caused substantial increases in heart rate but only slight increases in blood pressure. Injection of the GABA agonist muscimol prior to treatment with L-allylglycine prevented these cardiovascular changes. In another series of experiments, levels of GABA in the posterior hypothalamus and adjacent areas were measured 90 min after unilateral injection of L-allylglycine (12.5 or 25 micrograms), D-allylglycine (25 micrograms) or saline into the posterior hypothalamus. Only L-allylglycine caused increases in heart rate and blood pressure and decreases in levels of GABA. Quantitatively, the increases in heart rate at sacrifice were strongly correlated with the decreases in levels of GABA in the injected posterior hypothalamus (r = -0.94; P less than 0.002) but not in other regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Abshire
V M
VM
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46223.
Hankins
K D
KD
Roehr
K E
KE
DiMicco
J A
JA
D000501:Allylglycine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives*; D006339:Heart Rate / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000501:Allylglycine; D005680:gamma-Aminobutyric Acid; D005998:Glycine