Catalpol regulates cholinergic nerve system function through effect on choline acetyl-transferase not M receptor affinity

Abstract

ObjectiveTo explore the effect of catalpol on choline acetyl-transferase and M receptor affinity in a PC12 cell model and a rat model induced by beta-amyloid 25–35 (Aβ25–35). MethodsIn PC12 cells, catalpol (10μmol/l, 100μmol/) or saline was retained in the medium and Aβ25–35 (final concentration 20μmol/l) was added. Choline acetyl-transferase (ChAT) expression was determined by immunocytochemistry, ChAT activity measured by radioenzymatic assay, and M receptor (muscarinic receptor) affinity determined by 3H-QNB binding test. In Wistar rats, Aβ25–35 was injected intracerebroventricularly to establish AD model. After injection of Aβ25–35, the rats were injected catalpol at 5 and 10mg/kgd−1 intraperitoneally for the next 7 days, and saline for the control rats. ChAT expression, ChAT activity and M receptor affinity were tested. Cells and rats all were divided into four groups: Group A (control), Group B (model), Group C (catalpol low dose), and Group D (catalpol high dose). ResultsCompared with control, both PC12 cell and rat AD models showed decreased expression and activity of ChAT (p<0.01), but M receptor affinity remained the same (p>0.05). Compared with model group, treatment of catalpol increased expression and activity of ChAT of PC12 cell and rat AD model induced by Aβ25–35, p<0.05 or p<0.01 respectively. But there was no difference of M receptor affinity among the four groups (p>0.05). M receptor affinity remained the same as concentration of catalpol increased gradually in atropine competition experiments (p>0.05). ConclusionsCatalpol could regulate the cholinergic nerve system function from its effect on ChAT and may have beneficial effect for treatment of AD, but had no effect on M receptor affinity.