RT Journal Article
SR Electronic
T1 Binding of Atropine and Muscarone to Rat Brain Fractions and its Relation to the Acetylcholine Receptor
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 33
OP 40
VO 9
IS 1
A1 J. T. FARROW
A1 R. D. O’BRIEN
YR 1973
UL http://molpharm.aspetjournals.org/content/9/1/33.abstract
AB The binding of atropine and muscarone to subcellular fractions from whole rat brain was measured by equilibrium dialysis. At 10 nM, muscarone and atropine, but not decamethonium, dimethyltubocurarine, or nicotine, bound to a crude mitochondrial fraction from brain, and the binding was reversible. Atropine and muscarone at 10 nM did not bind to homogenates of kidney or lung. Atropine, but not muscarone, bound to liver homogenates and liver mitochondria, probably to atropinesterase. Atropine at 10 nM bound to a greater extent, on a protein basis, to fractions enriched in synaptosomes, pre- and postsynaptic membranes, and membrane of uncertain origin, than to other fractions. Muscarone showed a similar binding profile but also bound to purified mitochondrial fractions. Atropine bound to the synaptic membrane fraction at two sites present at 0.089 ± 0.018 and 0.91 ± 0.20 nmole/g of tissue (fresh weight), with binding constants of 0.6 ± 0.01 nM an d 0.9 ± 0.18 µM, respectively. Only scopolamine, of the sixteen drugs tested (at 50 nM), interfered with atropine binding at 5 nM to the same fraction. These findings are interpreted as showing that the higher-affinity site for atropine binding is the site more likely to be related to the physiological acetylcholine receptor. ACKNOWLEDGMENTS We wish especially to thank Drs. M. E. and A. T. Eldefrawi for their generous advice. We also wish to thank Dr. H. Howland for computer analysis. We are grateful to the Geigy Company of Switzerland for donating normuscarone, and to Mr. B. D. Hilton for synthesizing [3H]muscarone.