Central alpha/sub 2/ adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve

Thesis/Dissertation · Wed Jan 01 00:00:00 EST 1986

OSTI ID:6720432

Adler, C H

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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DOSE-RESPONSE RELATIONSHIPS
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CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
DECOMPOSITION
DRUGS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
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ISOTOPE APPLICATIONS
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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
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