Dual aminergic regulation of central beta adrenoceptors. Effect of atypical antidepressants and 5-hydroxytryptophan

Journal Article · Thu Jun 01 00:00:00 EDT 1989 · Neuropsychopharmacology; (United States)

DOI:https://doi.org/10.1016/0893-133X(89)90011-0· OSTI ID:5822556

Manier, D H; Gillespie, D D; Sulser, F

Nonlinear regression analysis of agonist competition binding curves reveals that the (/sup 3/H)-dihydroalprenolol-labeled receptor population with low affinity for isoproterenol is increased by p-chlorophenylalanine (PCPA) and this increase is abolished by 5-hydroxytryptophan (5-HTP) in vivo. Desipramine (DMI) decreased the beta adrenoceptor population with high agonist affinity to the same degree in PCPA-treated animals as in control animals, thus explaining the reported discrepancy between beta adrenoceptor number and responsiveness of the beta adrenoceptor-coupled adenylate cyclase system. Mianserin also selectively reduced the beta adrenoceptor population with high agonist affinity in membrane preparations of normal animals, whereas fluoxetine selectively abolished the upregulation of the low affinity sites in reserpinized animals and had no effect on either receptor population from brain of normal animals. The results emphasize the importance of nonlinear regression analysis of agonist competition binding for the interpretation of drug action and encourage the pursuit of the molecular neurobiology of the serotonin (5-HT)/norepinephrine (NE) link in brain.

• Research Organization: Vanderbilt Univ. School of Medicine, Nashville, TN (USA)
• OSTI ID: 5822556
• Journal Information: Neuropsychopharmacology; (United States), Vol. 2:2
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTIDEPRESSANTS
BIOCHEMICAL REACTION KINETICS
HYDROXYTRYPTOPHAN
SYMPATHOMIMETICS
RECEPTORS
AFFINITY
BIOLOGICAL MODELS
CELL MEMBRANES
RATS
REGRESSION ANALYSIS
RESERPINE
SEROTONIN
SYMPATHOLYTICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALOIDS
AMINES
AMINO ACIDS
ANIMALS
ANTIHYPERTENSIVE AGENTS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
CARBOXYLIC ACIDS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM AGENTS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATHEMATICS
MEMBRANE PROTEINS
MEMBRANES
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PSYCHOTROPIC DRUGS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RODENTS
STATISTICS
TRYPTAMINES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques