Characteristics of muscarinic acetylcholine receptors in rat brain.
Characteristics of muscarinic acetylcholine (ACh) receptors were studied in the rat central nervous system (CNS) using 3H-quinuclidinyl benzilate (QNB), an antagonist of muscarinic ACh receptors. Scatchard analysis indicated that the rat CNS had a single 3H-QNB binding site with an apparent dissociation constant (Kd) of 5.0 X 10(-10) M. Li+, Zn++ and Cu++ had strong effects on 3H-QNB binding which indicates that these metal ions might play important roles at muscarinic ACh receptor sites in the brain. Since antidepressants and antischizophrenic drugs displaced the binding of 3H-QNB, the anticholinergic effects of these drugs need to be taken into account when they are applied clinically. The muscarinic ACh receptor was successfully solubilized with lysophosphatidylcholine. By gel chromatography, with a Sepharose 6B column, the solubilized muscarinic ACh receptor molecule eluted at the fraction corresponding to a Stokes' radius of 6.1 nm. With the use of sucrose-density-gradient centrifugation, the molecular weight of the solubilized muscarinic ACh receptor was determined to be about 90,000 daltons. The regional distribution of 3H-QNB binding in rat brain was examined, and the highest level of 3H-QNB binding was found to be in the striatum followed by cerebral cortex and hippocampus, indicating that muscarinic ACh mechanisms affect CNS function mainly through these areas.
D000818:Animals; D001923:Brain Chemistry; D002712:Chlorides / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008970:Molecular Weight; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000032:analysis*; D011976:Receptors, Muscarinic / Q000032:analysis*; D014316:Tritium; D015032:Zinc / Q000494:pharmacology
D002712:Chlorides; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D015032:Zinc