triethyllead and trimethyltin

Effects of several alkylmetals on free intrasynaptosomal Ca2+ concentration, [Ca2+]i, were studied in vitro using the fluorescent Ca2+ indicator fura-2. Neurotoxic alkylmetals methylmercury (Met-Hg), triethyllead (TEL), triethyltin (TET), and trimethyltin (TMT) (at 2.5-30 microM) increased [Ca2+]i to different degrees. Met-Hg was the most potent, elevating [Ca2+]i 100-800 nM, dose dependently and significantly more than high K+ (150 nM) or veratridine (350 nM). The effect of Met-Hg could not be inhibited with a Ca2+ channel blocker, verapamil, nor with a Na+ channel blocker, tetrodotoxin. Inhibition of the mitochondrial Ca2+ uptake in situ with rotenone + oligomycin decreased the potency of Met-Hg to elevate [Ca2+]i but did not change the resting [Ca2+]i. Met-Hg also slightly decreased synaptosomal ATP. TEL and TET elevated [Ca2+]i by 100-200 nM. The effect of TEL, but not that of TET, could be blocked with verapamil (36%) and veratridine (67%). TEL was less efficient in the presence of ouabain. Neither TEL nor TET had significant mitochondrial effects in situ contributing to [Ca2+]i. TMT increased [Ca2+]i less than TET while dimethyltin and methyltin were inactive. These results indicate that neurotoxic derivatives of alkylmetals studied increase [Ca2+]i. This occurs mainly either by nonspecific increase (Met-Hg, TET) of Ca2+ leakage through the plasma membrane and/or specific interference with the mechanisms regulating Ca2+ fluxes through the plasma membrane (TEL).

Topics: Adenosine Triphosphate; Animals; Calcium; Dose-Response Relationship, Drug; Ion Channels; Male; Mathematics; Methylmercury Compounds; Mitochondria; Oligomycins; Organometallic Compounds; Ouabain; Rats; Rats, Inbred F344; Rotenone; Synaptosomes; Tetrodotoxin; Trialkyltin Compounds; Triethyltin Compounds; Trimethyltin Compounds; Veratridine

The effect of various organic metal compounds on delta-aminolevulinic acid dehydratase (ALAD, porphobilinogen synthetase) activity has been studied. Various organic tin and lead compounds have little effect on this enzyme. However, triethyl lead chloride has a potency similar to that of inorganic lead nitrate in inhibiting ALAD both for in vitro study and after in vivo dosing. Liver and blood ALAD have a similar sensitivity to lead compounds, which is reduced in the presence of zinc. Trimethyl lead chloride inhibits ALAD in vitro to a lesser extent. The results suggest that amphiphilic organic lead compounds may directly inhibit ALAD without prior degradation to inorganic lead. The diffusibility and persistence of triethyl lead combine to make it an especially hazardous lead compound.

Topics: Animals; Blood; Lead; Liver; Male; Nitrates; Organometallic Compounds; Porphobilinogen Synthase; Rats; Rats, Inbred F344; Trimethyltin Compounds