Acetylcholine synthesis in human CSF: Implications for study of central cholinergic metabolism
Tóm tắt
Investigation of neurological diseases involving central cholinergic dysfunction has led to numerous studies seeking a peripheral marker of cholinergic activity in brain. The main objective of these studies was to determine whether the ACh synthesizing activity present in human CSF was due to the presence of the enzyme choline acetyltransferase (ChAT; 68kDa). When CSF was fractionated into low and high molecular weight (Mr) components, 80% of the ACh synthesizing activity (AChSA) was found to be associated with the fraction <10 kDa. The remaining 20% was evenly distributed among fractions in the 5–30, 30–50, 50–300, and 300 kDa fractions. Although boiling destroyed all activity >10 kDa, the ChAT inhibitor NVP, at concentrations equal to or greater than that required to inhibit ChAT in human cortical tissue, did not alter the ACh-SA in either fraction. Results indicate that normal human CSF does not contain ChAT and all ACh-SA in CSF reflects non-enzymatic imidazole/histidine-like catalyzed synthesis.
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