INTERACTION OF METALS WITH MUSCARINIC CHOLINOCEPTOR AND ADRENOCEPTOR BINDING, AND AGONIST-STIMULATED INOSITOL PHOSPHOLIPID HYDROLYSIS IN RAT-BRAIN

In vitro mercury (Hg) or lead (Pb) effectively inhibited the binding o f H-3-quinuclidinyl-benzilate (QNB) (a muscarinic cholinoceptor antago nist) and H-3-prazosin (an alpha(1)-adrenoceptor antagonist) to their receptors in cerebellar and cerebral cortex membranes in a concentrati on-dependent manner. Hg was more potent than Pb. When the rats were tr eated with Hg (5 mg/kg body wt) or Pb (25 mg/kg body wt) for 24 hr, a decrease in H-3-prazosin and an increase in H-3-QNB receptor binding w ere observed in cerebral cortex. There was no alteration in H-3-prazos in binding in cerebellum with the above treatment of metals, but H-3-Q NB binding in cerebellum was significantly inhibited by Hg. However, b oth H-3-prazosin and H-3-QNB receptor bindings were significantly decr eased in cerebellum of rats treated for 7 days with Hg (1 mg/kg body w t/day) or Pb (25 mg/kg body wt/day). But in cerebral cortex of rats cr eated with these metals for 7 days, a decrease in H-3-prazosin and an increase in H-3-QNB receptor binding activities were noticed. There wa s a significant decrease in phospholipid content in cerebral cortex bu t not in cerebellum of rats treated with these metals for 7 days. At 1 00 mu M concentration carbachol or acetylcholine or norepinephrine sti mulated H-3-inositol incorporation and H-3-inositol phosphate (IF) for mation in rat cerebral cortical slices. Hg or Pb in vitro though incre ased the agonist-stimulated H-3-inositol incorporation, H-3-IP formati on was not significantly altered. The present investigation demonstrat es the differential responses by alpha(1)-adrenoceptor and muscarinic cholinoceptor in cerebellum and cerebral cortex of rat to in vitro and in vivo effects of Hg or Pb. (C) 1991 Elsevier Science Inc.