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

Abstract

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.

Authors:
Publication Date:
Research Org.:
Indiana Univ.-Purdue Univ., Indianapolis (USA). Div. of Neuropathology
OSTI Identifier:
5742081
Resource Type:
Thesis/Dissertation
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

Knepper, S.M. Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs. United States: N. p., 1985. Web.
Knepper, S.M. Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs. United States.
Knepper, S.M. Tue . "Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs". United States.
@article{osti_5742081,
title = {Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs},
author = {Knepper, S.M.},
abstractNote = {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.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Jan 01 00:00:00 EST 1985},
month = {Tue Jan 01 00:00:00 EST 1985}
}

Thesis/Dissertation:
Other availability
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