Increase of choline acetyltransferase by colchicine in primary cell cultures of spinal cord.
Colchicine (5-10 microM) increased choline acetyltransferase (ChAT) activity 5-10-fold and suppressed acetylcholinesterase (AChE) and glutamate decarboxylase (GAD) activities to 30% and 50%, respectively, of the levels of control cells in mouse spinal cord cells cultured for several days. The synthesis of radiolabeled acetylcholine (ACh) from [14C]choline was also enhanced 4.6-fold, although the uptake of [14C]choline into cells was decreased to 80% of control level. Neither the incorporation of [3H]leucine into protein nor the total amount of protein was increased by colchicine. Vinblastine also increased ChAT activity while cytochalasin B was not effective. Immunochemical titration study revealed that the increase of ChAT activity by colchicine was due to the accumulation of ChAT molecules. Co-culture of spinal cord cells with skeletal muscle markedly stimulated ChAT activity, and the addition of colchicine to the cocultures showed greater than additive effect. These observations indicate that colchicine increases ChAT molecules in a specific manner, that the stimulatory effect of colchicine on ChAT activity is possibly mediated via the interaction with microtubules, and that the increase of ChAT activity is based on a mechanism different from that of co-cultures with skeletal muscle cells.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D005968:Glutamate Decarboxylase; D002794:Choline; D003078:Colchicine