Sodium-independent, bicuculline-sensitive (/sup 3/H)GABA binding to isolated rat hepatocytes
To determine whether hepatocytes possess specific receptor sites for gamma-aminobutyric acid (GABA), a potent amino acid neurotransmitter, (/sup 3/H)GABA, was added to sodium-free suspensions of Percoll-purified hepatocytes derived from collagenase-perfused rat livers under various experimental conditions and in the presence or absence of specific GABA receptor agonists (muscimol) and antagonists (bicuculline). The effects of GABA, muscimol, and bicuculline on hepatocyte resting membrane potentials were also determined. Specific binding of (/sup 3/H)GABA to hepatocytes was a consistent finding. GABA-hepatocyte interactions were reversible and temperature dependent. Muscimol and bicuculline inhibited binding in a dose-dependent manner (IC50, 30 nM and 50 microM, respectively), whereas strychnine (1.0-100 microM), a nonspecific central nervous system stimulant, had no appreciable effect. Both GABA and muscimol (100 microM) caused significant hyperpolarization of hepatocyte resting membrane potential (delta PD 5.4 +/- 3.1 and 22.2 +/- 16.2 mV, respectively, means +/- SD, P less than 0.0005). Bicuculline (100 microM) inhibited the effect of muscimol (P less than 0.05). The results of this study suggest that specific GABA receptor sites exist on the surface of isolated rat hepatocytes. The presence of such sites raises the possibility that, in addition to adrenergic and cholinergic innervation, hepatic function may be influenced by GABA-ergic neurotransmitter mechanisms.
- Research Organization:
- Univ. of Calgary, Alberta
- OSTI ID:
- 6355395
- Journal Information:
- Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AMINOBUTYRIC ACID
BIOCHEMICAL REACTION KINETICS
RECEPTORS
ANALEPTICS
CELL MEMBRANES
DOSE-RESPONSE RELATIONSHIPS
ELECTROPHYSIOLOGY
LIVER CELLS
RATS
SODIUM
TEMPERATURE DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALI METALS
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM AGENTS
DRUGS
ELEMENTS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
METALS
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHYSIOLOGY
PROTEINS
REACTION KINETICS
RODENTS
SOMATIC CELLS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques