Species dependent dual modulation of the benzodiazepine/GABA receptor chloride channel by dihydroergosine
- Rudjer Boskovic Institute, Zagreb (Yugoslavia)
Dihydroergosine enhanced the incidence of bicuculline induced convulsions in female rats, while 100 mg/kg of dihydroergosine given to female mice made 45% convulsive dose of bicuculline to be subconvulsive. The same dose of dihydroergosine enhanced in mice the latency of bicuculline-induced convulsions. Although, in in vitro experiments dihydroergosine showed very weak ability to prevent the binding of {sup 3}H-muscimol, the drug was able to diminish and to augment the IC{sub 50} of bicuculline and GABA when added to crude synaptosomal pellet of the rat and mouse brain respectively. Lower concentrations of dihydroergosine stimulated and higher inhibited {sup 3}H-TBOB binding to the crude synaptosomal pellet of the rat brain. In the preparation of mouse brain dihydroergosine produced only inhibition of {sup 3}H-TBOB binding. Only slight quantitative differences were observed in bicuculline-induced stimulation and in GABA- and diazepam-induced inhibition of {sup 3}H-TBOB binding between the two species. The results suggest that the opposite species-dependent effects of dihydroergosine on bicuculline-induced convulsions are due to the ability of this drug to modulate species-dependently the benzodiazepine/GABA receptor chloride channel complex.
- OSTI ID:
- 6796091
- Journal Information:
- Life Sciences; (USA), Journal Name: Life Sciences; (USA) Vol. 47:6; ISSN LIFSA; ISSN 0024-3205
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL VARIABILITY
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CHLORIDES
CHLORINE COMPOUNDS
DRUGS
GENETIC VARIABILITY
HALIDES
HALOGEN COMPOUNDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MICE
NERVE CELLS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES