Acute effects of lead at central synapses in vitro.
The acute effects of lead in the rat CNS in vitro were studied on synaptic transmission in the isolated hemisected spinal cord from newborn rats and on the transport of exogenous GABA, acetylcholine and cis-3-aminocyclohexane carboxylic acid (ACHC) from slices of cerebral cortex from adult rats. Lead had quite variable effects on monosynaptic reflexes and synaptic potentials. When it occurred, the depression of synaptic transmission by lead (typically at 18.5 mumol/liters of added lead acetate) was reversible provided exposure times were less than 15 min; furthermore, depression could be antagonised by increasing the external calcium concentration. Lead had no effect on the postsynaptic responses of motoneurons to the putative transmitters L-glutamate, GABA and glycine or to eledoisin-related peptide. The effects of lead on uptake and release of exogenous GABA and ACHC were dependent on the perfusion buffer employed: minimal effects were seen in solutions buffered with either phosphate or carbonate. When Tris HCl was used as buffer, lead inhibited the uptake of GABA and potentiated the spontaneous release of GABA with an EC50 = 50 mumol/liters as added lead acetate. In Tris HCl buffer, lead acetate (100 mumol/liters) produced a two-fold enhancement in the spontaneous release of acetylcholine under conditions where choline and acetylcholine re-uptake was blocked by hemicholinium. The availability of free lead cations in solution is highly dependent on the concentrations of other ions (particularly phosphates) and the pH. Under the appropriate conditions, lead can inhibit CNS synaptic function acutely in a manner consistent with lead competing with calcium ions in transmitter release processes as has been established for acetylcholine release at peripheral synapses.
Spence
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I
Drew
C
C
Johnston
G A
GA
Lodge
D
D
D000109:Acetylcholine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000598:Amino Acids, Cyclic; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects*; D003509:Cyclohexanecarboxylic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D003509:Cyclohexanecarboxylic Acids; D007854:Lead; C015666:3-aminocyclohexanecarboxylic acid; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine