Developmental studies of the uptake of choline, GABA and dopamine by crude synaptosomal preparations after in vivo or in vitro lead treatment. 1980

P B Ramsay, and M R Krigman, and P Morell

The kinetics of sodium dependent, high affinity uptake of choline and dopamine by striatal synaptosomal preparations and of GABA (gamma-aminobutyric acid) by cortical synaptosomal preparations have been examined during the development of Long-Evans control and lead-treated rats. Choline uptake was very low until 12 days postnatally, then the Vmax increased and approached adult values of 29 pmol/mg prot./min within a week. GABA uptake was somewhat elevated at birth and only after three weeks did it decrease to the adult value of 0.7 nmol/mg prot./min. Dopamine uptake was low at birth, developed linearly with age and by 30 days postnatally approached the adult value of 68 pmoles/mg prot./min. The high affinity uptake constants (choline, 0.66 microM; GABA, 4.4 muM; and dopamine, 0.31 muM) did not change markedly during development. Similar studies were conducted with rats treated at the highest lead dosage which did not result in weight loss (100 microgram lead as lead acetate/g body weight/day via intubation). Blood and brain lead determinations confirmed a substantial lead exposure. Such chronic exposure did not markedly affect the amount or developmental pattern of uptake of the putative neurotransmitters. The effect of 2.5 x 10(-5) M lead acetate in vitro on the kinetics of high affinity uptake of these compounds into preparations from 20-26-day-old rats was investigated. When uptake was assayed in the absence of calcium, lead caused a 20% increase in the Vmax for dopamine. This stimulation was reduced if samples were assayed in the presence of n mM CaCl2. The Km for high affinity uptake of these neurotransmitter-related compounds was not affected by lead. In other studies, crude synaptosomal preparations were preloaded with neurotransmitter by preincubation with radioactive choline, GABA, or dopamine. Release of radioactive neurotransmitter, either spontaneous or in response to potassium depolarization, was quantitated and correlated with the presence or absence of 2.5 x 10(-5) M lead and/or 10(-3) M calcium ions. Lead slightly inhibited calcium dependent spontaneous release of dopamine. Lead also appeared to partially substitute for calcium in the potassium depolarized release of dopamine and GABA, although subtraction of the spontaneous (potassium independent) component reduced the magnitude of the lead effect.

UI MeSH Term Description Entries
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010042 Ouabain A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE. Acocantherin,G-Strophanthin,Acolongifloroside K,G Strophanthin
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D002794 Choline A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. Bursine,Fagine,Vidine,2-Hydroxy-N,N,N-trimethylethanaminium,Choline Bitartrate,Choline Chloride,Choline Citrate,Choline Hydroxide,Choline O-Sulfate,Bitartrate, Choline,Chloride, Choline,Choline O Sulfate,Citrate, Choline,Hydroxide, Choline,O-Sulfate, Choline
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D006426 Hemicholinium 3 A potent inhibitor of the high affinity uptake system for CHOLINE. It has less effect on the low affinity uptake system. Since choline is one of the components of ACETYLCHOLINE, treatment with hemicholinium can deplete acetylcholine from cholinergic terminals. Hemicholinium 3 is commonly used as a research tool in animal and in vitro experiments. Hemicholinium

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