Developmental studies of the uptake of choline, GABA and dopamine by crude synaptosomal preparations after in vivo or in vitro lead treatment.
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.
D000375:Aging; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight; D001921:Brain / Q000254:growth & development; D002540:Cerebral Cortex / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006426:Hemicholinium 3 / Q000494:pharmacology; D009929:Organ Size; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D006426:Hemicholinium 3; D005680:gamma-Aminobutyric Acid; D010042:Ouabain; D002794:Choline; D004298:Dopamine