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 of 3H-quinuclidinyl-benzilate (QNB) (a muscarinic cholinoceptor antagonist) and 3H-prazosin (an alpha 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 microM 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 alpha 1-adrenoceptor and muscarinic cholinoceptor in cerebellum and cerebral cortex of rat to in vitro and in vivo effects of Hg or Pb.
Rajanna
B
B
Department of Biological Sciences, Alcorn State University, Lorman, MS 39096, USA. brajanna@lorman.alcorn.edu
Chetty
C S
CS
Rajanna
S
S
Hall
E
E
Fail
S
S
Yallapragada
P R
PR
D018674:Adrenergic Antagonists / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D007854:Lead / Q000494:pharmacology*; D008297:Male; D008628:Mercury / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D018674:Adrenergic Antagonists; D007295:Inositol Phosphates; D018727:Muscarinic Antagonists; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D007854:Lead; D011813:Quinuclidinyl Benzilate; D008628:Mercury; D011224:Prazosin