Benzodiazepines: rat pinealocyte binding sites and augmentation of norepinephrine-stimulated N-acetyltransferase activity
Studies of (/sup 3/H)diazepam binding to intact rat pineal cells were carried out in tissue culture preparations. The binding was saturable, reversible and proportional to the number of cells used. Scatchard analysis resulted in a linear plot (Kd . 23 nM, maximum binding sites (Bmax) . 1.56 pmol/mg of protein for cells in monolayer culture; Kd . 7 nM, Bmax . 1.3 pmol/mg of protein for cells in suspension culture). Inhibition constants (Ki) for clonazepam (500 nM), flunitrazepam (38 nM) and Ro-5-4864 (5 nM) indicated that the binding sites were probably of the ''peripheral'' type. In addition, the effects of diazepam on norepinephrine-stimulated N-acetyltransferase (NAT) activity were studied in organ culture and dissociated cell culture. Diazepam (10-50 microM) both prolonged and increased the magnitude of the norepinephrine-induced increase in NAT activity but did not affect the initial rate of rise of enzyme activity. The effect was dose-dependent and was also seen with clonazepam, flunitrazepam and Ro-5-4864, but not with Ro-15-1788. Diazepam, by itself, at these concentrations, had no effect on NAT, but enzyme activity was increased by higher concentrations (0.1-1 mM). Although a relationship between the (/sup 3/H)diazepam binding sites described here and the effect of benzodiazepines on NAT cannot be established from these studies, the data suggest that the benzodiazepines may alter melatonin levels through their action on NAT.
- Research Organization:
- Columbia Univ., New York, NY
- OSTI ID:
- 6722404
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Vol. 228:2
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ORGANIC NITROGEN COMPOUNDS
BIOLOGICAL EFFECTS
RECEPTORS
TRANSFERASES
ENZYME ACTIVITY
CELL CULTURES
MELATONIN
NORADRENALINE
PINEAL GLAND
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
DRUGS
ENZYMES
GLANDS
HETEROCYCLIC COMPOUNDS
HORMONES
INDOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PYRROLES
RODENTS
STEROID HORMONES
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550201 - Biochemistry- Tracer Techniques