Adenosine receptor modulation of seizure susceptibility in rats
Adenosine is considered to be a neuromodulator or cotransmitter in the periphery and CNS. This neuromodulatory action of adenosine may be observed as an anticonvulsant effect. Dose-response curves for R-phenylisopropyladenosine (PIA), cycohexyladenosine (CHA), 2-chloroadenosine (2-ClAdo), N-ethylcarboxamidoadenosine (NECA) and S-PIA were generated against PTZ seizure thresholds in the rat. The rank order of potency for adenosine agonists to elevate PTZ seizure threshold was R-PIA > 2-ClAdo > NECA > CHA > S-PIA. R-PIA was approximately 80-fold more potent than S-PIA. This 80-fold difference in potency between the diasteriomers of PIA was consistent with an A{sub 1} adenoise receptor-mediated response. The anticonvulsant action of 2-ClAdo was reversed by pretreatment with theoplylline. Chronic administration of theophylline significantly increased the specific binding of {sup 3}H-cyclohexyladenosine in membranes of the cerebral cortex and cerebellum of the rat. Chronic exposure to theophylline produced a significant increase in the densities of both the high- and low-affinity forms of A{sub 1} adenosine receptors in the cerebral cortex.
- Research Organization:
- Oregon State Univ., Corvallis, OR (USA)
- OSTI ID:
- 5228979
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
ANIMALS
AROMATICS
AZAARENES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PROTEINS
PURINES
RATS
REACTION KINETICS
RECEPTORS
RIBOSIDES
RODENTS
THEOPHYLLINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASODILATORS
VERTEBRATES
XANTHINES