Drug-induced regulation of 1,4-dihydropyridine Ca sup 2+ channel antagonist binding sites in the brain and heart
The ability of drugs to regulate the voltage-sensitive Ca{sup 2+} channels were assessed by determining the bind of ({sup 3}H)dihydropyridine Ca{sup 2+} channel antagonists in the heart and brain following administration of these drugs to rats and mice. Mice and rats implanted with morphine pellets for 3 days showed an increase in dihydropyridine binding sites in the brain, compared to non-treated or placebo treated controls. No increase in dihydropyridine binding sites was observed in the heart. The significance of the increase in binding to physical dependence on morphine is implied from the findings that pretreatment with Ca{sup 2+} channel antagonist drugs led to an attenuation of naloxone-precipitated withdrawal signs in both dependent rats and mice. Administration of other drugs, known to depress the CNS, was undertaken to determine whether the changes observed with morphine was a nonspecific response of the brain to depressant drugs. Prolonged administration of reserpine to rats resulted in no changes in dihydropyridine binding sites in the brain, even though the {beta}-adrenergic receptors in this tissue are upregulated. However, reserpine decreased the density of ({sup 3}H)nimodipine binding sites in the heart of this is accompanied by concomitant increases in {beta}-adrenergic receptors.
- Research Organization:
- Maryland Univ., Baltimore, MD (USA)
- OSTI ID:
- 5601111
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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MORPHINE
BIOCHEMICAL REACTION KINETICS
PORINS
RECEPTORS
RESERPINE
BRAIN
ENZYME INHIBITORS
HEART
MICE
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALOIDS
ANALGESICS
ANIMALS
ANTIHYPERTENSIVE AGENTS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BODY
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
NARCOTICS
NERVOUS SYSTEM
OPIUM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRROLES
REACTION KINETICS
RODENTS
SYMPATHOLYTICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques