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.</p

Improvement in freezing phenomenon of Parkinson's disease after DL-threo-3, 4-dihydroxyphenylserine.

A 77-year-old man with Parkinson's disease of long standing, under treatment with L-DOPA and benserazide, was administered DL-threo-3, 4-dihydroxyphenylserine (DL-threo-DOPS), a precursor of norepinephrine, for 10 days. With this administration the patient's freezing phenomenon was remarkably improved, and his dysarthria also showed improvement. When DL-threo-DOPS was suspended, the frozen gait returned on the third day to almost the former level, even though he continued to receive L-DOPA and benserazide. After administration of DL-threo-DOPS, the CSF level of 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of norepinephrine, was 127.5% of the pretreatment level. These observations suggest that DL-threo-DOPS can pass through the blood-brain barrier and change to norepinephrine, and that DL-threo-DOPS may be beneficial in the treatment of the freezing phenomenon of Parkinson's disease.</p