Effects of cyclodiene compounds on calcium pump activity in rat brain and heart.

The in vitro and in vivo effects of aldrin, dieldrin, and endrin on calmodulin regulated Ca2+-pump activity in rat brain synaptosomes and heart sarcoplasmic reticulum were investigated. All the 3 cyclodiene compounds inhibited both brain synaptosomal and heart sarcoplasmic reticulum Ca2+-pump activity in vitro in a concentration dependent manner. Calmodulin depleted Ca2+-pump activity was insensitive to the action of toxic compounds. Oral administration of pesticides (0.5-10 mg/kg) to rats similarly decreased the Ca2+-pump activity, in addition to decreasing the levels of calmodulin of both brain and heart thus indicating disruption in membrane Ca2+ transport mechanisms. Exogenous addition of calmodulin (1-20 micrograms) could effectively reverse the pesticide induced inhibition. Ca2+-pump activity is more sensitive to the 3 cyclodiene compounds in brain than in heart. The results of the present study indicate that the cyclodiene compounds may produce neurotoxic effects by altering calmodulin regulated calcium dependent events in neurons.

Effects of methyl mercury and cadmium on the kinetics of substrate activation of (K+)-paranitrophenyl phosphatase.

Previous studies from this laboratory have indicated that methyl mercuric chloride (CH3HgCl) and cadmium chloride (CdCl2) are potent inhibitors of K+-p-nitrophenyl phosphatase (K+-PNPPase). The present studies were undertaken to study the effects of CH3HgCl and CdCl2 on the substrate activation kinetics of K+-PNPPase to understand the mechanism of inhibition of Na+ pump by these heavy metals. Uncompetitive inhibition with regard to activation by PNPP was indicated by altered Vmax and Km values by both the heavy metals. Substrate activation kinetics of heavy metal inhibited K+-PNPPase in the presence of 25 microM dithiothreitol and glutathione indicated mixed type of activation by altering apparent Vmax and Km. Absence of competition between PNPP site and heavy metals appear to indicate absence of reactive-SH groups in the active site. Failure of added iodacetate, in concentrations ranging from 5 X 10(-8) to 5 X 10(-5) M, to inhibit K+-PNPPase further substantiate this conclusion. The results suggest that CH3HgCl and CdCl2 inhibit Na+ pump by inducing conformational changes in the enzyme and thereby decrease catalytic velocity of dephosphorylation of the enzyme-phosphoryl complex. Hydrolysis of PNPP was linear with time with or without either heavy metal and the inhibition exerted by CH3HgCl or CdCl2 on free or heavy metal loaded enzyme indicated absence of heavy metal interaction. The results suggest that CH3HgCl and CdCl2 inhibit K+-PNPPase possibly by binding at two different sites.

In vivo effects of toxaphene on calmodulin-regulated calcium-pump activity in rat brain.

In vivo effect of toxaphene on calcium pump activity in rat brain P2 fraction was studied. Male Sprague-Dawley rats (200-250 g) were dosed with toxaphene at 0, 25, 50, and 100 mg/kg X d for 3 d and sacrificed 24 h after last dose. Ca2+-ATPase activity and 45Ca2+ uptake were determined in brain P2 fraction. Toxaphene decreased both Ca2+-ATPase activity and 45Ca2+ uptake, and the reduction was dose-dependent. Both substrate and Ca2+ activation kinetics of Ca2+-ATPase indicated noncompetitive type of inhibition, as evidenced by decreased catalytic velocity but not enzyme-substrate affinity. The decreased Ca2+-ATPase activity and 45Ca2+ uptake were restored to normal level by exogenously added calmodulin, which increased both velocity and affinity. The inhibition of Ca2+-ATPase activity and 45Ca2+ uptake and restoration by calmodulin suggests that toxaphene may impair active calcium transport mechanisms by decreasing levels of calmodulin.

Changes in respiration and ionic content in tissues of freshwater mussel exposed to methyl parathion toxicity.

Oxygen consumption and sodium, potassium and calcium concentration were determined in the freshwater mussel, Lamellidens marginalis, and its tissues during methyl parathion (MP) toxicity. A transient increase followed by decrease in whole animal or tissue respiration as a function of time was observed. Greater loss of calcium by the mantle, sodium by the gill, and calcium and sodium by the hepatopancreas and foot was observed. As compared to calcium and sodium, the loss of potassium by the tissues was less.