Central alpha/sub 2/ adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve
The alpha/sub 2/ adrenergic receptor subtype is thought to play a role in the mechanism of action of antidepressant and antihypertensive drugs. This thesis has attempted to shed light on the regulation of central alpha/sub 2/ adrenergic receptors in the rat cerebral cortex. Repopulation kinetics analysis allows for the determination of the rate of receptor production, rate constant of degradation, and half-life of the receptor. This analysis was carried out using both radioligand binding and functional receptor assays at various times following the irreversible inactivation of central alpha/sub 2/ adrenergic receptors by in vivo administration of N-ethoxycarbonyl-2-ethyoxy-1,2-dihydroquinoline (EEDQ). Both alpha/sub 2/ agonist and antagonist ligand binding sites recovered with a t/sub 1/2/ equal to approximately 4 days. The function of alpha/sub 2/ adrenergic autoreceptors, which inhibit stimulation-evoked release of /sup 3/H-norepinephrine (/sup 3/H-NE) and alpha/sub 2/ adrenergic heteroreceptors which inhibit stimulation-evoked release of /sup 3/H-serotonin (/sup 3/H-5-HT) were assayed. The t/sub 1/2/ for recovery of maximal autoreceptor and heteroreceptor function was 2.4 days and 4.6 days, respectively. The demonstration of a receptor reserve is critical to the interpretation of past and future studies of the alpha/sub 2/ adrenergic receptor since it demonstrates that: (1) alterations in the number of alpha/sub 2/ adrenergic receptor binding sites cannot be extrapolated to the actual function of the alpha/sub 2/ adrenergic receptor; and (2) alterations in the number of alpha/sub 2/ receptors is not necessarily accompanied by a change in the maximum function being studied, but may only result in shifting of the dose-response curve.
- Research Organization:
- New York Univ., NY (USA)
- OSTI ID:
- 6720432
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
RECEPTORS
BIOCHEMICAL REACTION KINETICS
SYMPATHOMIMETICS
RADIOIMMUNOASSAY
BIODEGRADATION
BIOSYNTHESIS
CELL PROLIFERATION
CEREBRUM
DOSE-RESPONSE RELATIONSHIPS
NORADRENALINE
PHYSIOLOGY
RATS
SEROTONIN
TRITIUM COMPOUNDS
ADRENAL HORMONES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
DECOMPOSITION
DRUGS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
IMMUNOASSAY
IMMUNOLOGY
INDOLES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRROLES
RADIOASSAY
RADIOIMMUNOLOGY
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RODENTS
STEROID HORMONES
SYNTHESIS
TRACER TECHNIQUES
TRYPTAMINES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
551001 - Physiological Systems- Tracer Techniques