Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs

Thesis/Dissertation · Tue Jan 01 00:00:00 EST 1985

OSTI ID:5742081

Knepper, S M

Norepinephrine-(NE) and calcium ionophore A23187-stimulated phosphoinositide (PIn) metabolism in rat brain slices was studied under varying calcium conditions. Tissue was labelled with /sup 3/H-myo-inositol and /sup 3/H-inositol phosphates (IPn), products of PIn metabolism were measured. In the absence of media calcium the response to NE was decreased while that to A23187 was little affected A23187 can release calcium from intracellular stores. Basal and stimulated accumulation of /sup 3/H-IPn was reversibly antagonized with EGTA by addition of calcium. Using calcium buffers, approximately 10/sup -7/ M free calcium was required to support hydrolysis. Free intracellular calcium is maintained at approximately this level. Thus calcium is required for PIn hydrolysis but appears to play a permissive role, basal levels being sufficient to support metabolism. Conformationally-defined (rigid) and -restricted (semi-rigid) analogs of the most stable conformations of amphetamine, antiperiplanar (exo) and gauche (endo), were utilized to probe the conformational requirements of vesicular NE transport. Analogs tested were 2-aminotetralin (2AT), 3-methyltetrahydroisoquinoline, anti- and syn-9-aminobenzobicyclo(2.2.1)heptene, and endo and exo conformers of 2-aminobenzobicyclo(2.2.1)heptene and 2-aminobenzobicyclo(2.2.2)octene.

• Research Organization: Indiana Univ.-Purdue Univ., Indianapolis (USA). Div. of Neuropathology
• OSTI ID: 5742081
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CALCIUM
BIOLOGICAL EFFECTS
INOSITOLS
METABOLISM
NORADRENALINE
MEMBRANE TRANSPORT
BRAIN
HYDROLYSIS
PHOSPHATES
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ALKALINE EARTH METALS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARBOHYDRATES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
DECOMPOSITION
DRUGS
ELEMENTS
HORMONES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LYSIS
MAMMALS
METALS
MONOSACCHARIDES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHOSPHORUS COMPOUNDS
RODENTS
SACCHARIDES
SOLVOLYSIS
STEROID HORMONES
SYMPATHOMIMETICS
VERTEBRATES
550501* - Metabolism- Tracer Techniques