veratrine and nipecotic-acid

Some characteristics of gamma aminobutyric acid (GABA) uptake and release in rat superior cervical ganglion (SCG) were investigated. Kinetic analysis of GABA uptake indicated the existence of both high affinity (Km = 18.6 microM) and low affinity (Km = 485 microM) uptake systems. 3H-GABA influx was decreased by inhibitors of glial (beta-alanine), neuronal (2,4-diaminobutyric acid, DABA), or glial and neuronal GABA uptake (nipecotic acid). 3H-GABA efflux was elicited by K+ depolarization in a dose-dependent manner, an effect unaltered by severing the preganglionic nerve fibers. Superfusion of SCG explants with DABA or beta-alanine resulted in increased 3H-GABA efflux from tissue, an effect amplified by the absence of calcium in the superfusion medium. 3H-GABA loading in the presence of DABA, but not in the presence of beta-alanine, resulted in abolition of K(+)-elicited 3H release. At 20 mM, but not at 50 mM K+, the release of 3H-GABA was inhibited by replacing Ca2+ by Mg2+ and by adding EGTA, or by incubating SCG in the presence of the Ca(2+)-channel blocker verapamil. Veratrine evoked GABA release in Ca(2+)-independent manner. None of several putative SCG autacoids or agonists (nicotine, muscarine, norepinephrine, dopamine, serotonin, baclofen, muscimol) significantly modified GABA release.

Topics: Acetanilides; Anesthetics, Local; Animals; beta-Alanine; Brain Chemistry; Calcium; Female; gamma-Aminobutyric Acid; Ganglia, Sympathetic; Kinetics; Male; Neurons; Neurotransmitter Agents; Nipecotic Acids; Proline; Rats; Rats, Wistar; Receptors, GABA-A; Veratrine

Cardiovascular effects of chemical stimulation of the rostral ventrolateral medulla were studied in pentobarbital-anesthetized, paralyzed rats to examine the medullary GABAergic mechanisms responsible for cardiovascular regulation. Bilateral microinjections of 3-mercaptopropionic acid (10 micrograms), an inhibitor of gamma-aminobutyric acid (GABA) synthesis, into the ventrolateral medulla produced an increase in blood pressure and heart rate. Unilateral microinjection of nipecotic acid (3 micrograms), a reuptake inhibitor of GABA, elicited a fall in arterial pressure and heart rate. Bilateral microinjections of bicuculline (100 pmol), a GABA antagonist, into the ventrolateral medulla produced a sustained increase in arterial pressure and heart rate and, in addition, inhibited the hypotensive action induced by veratrine (0.3 mg/kg, i.v.). Lesioning of the rat nucleus tractus solitarii did not alter GABA content in the rostral ventrolateral medulla. These results support the hypothesis that in the rostral ventrolateral medulla, there exist GABAergic mechanisms involved in cardiovascular regulation. It seems unlikely that the GABAergic mechanisms originate mainly from neurons in the nucleus tractus solitarii.

Topics: 3-Mercaptopropionic Acid; Animals; Bicuculline; gamma-Aminobutyric Acid; Hemodynamics; Male; Medulla Oblongata; Microinjections; Nipecotic Acids; Pressoreceptors; Proline; Rats; Rats, Inbred Strains; Veratrine