Interaction of Metals with Muscarinic Cholinoceptor and Adrenoceptor Binding, and Agonist-Stimulated Inositol Phospholipid Hydrolysis in Rat Brain

Abstract

In vitro mercury (Hg) or lead (Pb) effectively inhibited the binding of 3H-quinuclidinyl-benzilate (QNB) (a muscarinic cholinoceptor antagonist) and 3H-prazosin (an α 1-adrenoceptor antagonist) to their receptors in cerebellar and cerebral cortex membranes in a concentration-dependent manner. Hg was more potent than Pb. When the rats were treated with Hg (5 mg/kg body wt) or Pb (25 mg/kg body wt) for 24 hr, a decrease in 3H-prazosin and an increase in 3H-QNB receptor binding were observed in cerebral cortex. There was no alteration in 3H-prazosin binding in cerebellum with the above treatment of metals, but 3H-QNB binding in cerebellum was significantly inhibited by Hg. However, both 3H-prazosin and 3H-QNB receptor bindings were significantly decreased in cerebellum of rats treated for 7 days with Hg (1 mg/kg body wt/day) or Pb (25 mg/kg body wt/day). But in cerebral cortex of rats treated with these metals for 7 days, a decrease in 3H-prazosin and an increase in 3H-QNB receptor binding activities were noticed. There was a significant decrease in phospholipid content in cerebral cortex but not in cerebellum of rats treated with these metals for 7 days. At 100 μM concentration carbachol or acetylcholine or norepinephrine stimulated 3H-inositol incorporation and 3H-inositol phosphate (IP) formation in rat cerebral cortical slices. Hg or Pb in vitro though increased the agonist-stimulated 3H-inositol incorporation, 3H-IP formation was not significantly altered. The present investigation demonstrates the differential responses by α 1-adrenoceptor and muscarinic cholinoceptor in cerebellum and cerebral cortex of rat to in vitro and in vivo effects of Hg or Pb.