The effect of aluminum on muscarinic receptors in isolated cerebral microvessels.
Aluminum has been shown to alter transport and enzymatic functions of the blood-brain barrier. In this study, quinuclidinyl benzilate (QNB), a muscarinic antagonist, was used to quantitate possible changes in muscarinic receptor number and/or affinity in isolated cerebral microvessels treated with aluminum. The saturation binding isotherm showed an increase in QNB binding at each ligand concentration (0.031-0.25 nM) in the presence of 10 microM AlCl3. Scatchard analysis of this binding data indicated that microvessels treated with aluminum showed a significant increase (P less than 0.05) in maximum binding capacity (284 +/- 21.5 fmol/mg protein) relative to untreated controls (207 +/- 31 fmol/mg protein), but no change in receptor affinity. Incubation of 0.25 nM QNB with 0.1 microM-100 microM AlCl3 resulted in a dose-dependent increase in specific QNB binding that was statistically significant (P less than 0.05-0.01) at or above 1 microM AlCl3. These data demonstrate that aluminum can affect muscarinic cholinergic receptors present on cerebral endothelial cells and suggest that this metal ion may compromise the integrity of the biochemical blood-brain barrier.
Grammas
P
P
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City.
Caspers
M L
ML
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*
D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D000535:Aluminum