Enzymatic synthesis of a false cholinergic neurotransmitter: diethylaminoethyl acetate as a muscarinic agonist analog of acetylcholine.
Diethylaminoethyl acetate, an acetylcholine analog, was formed upon the incubation of diethylaminoethanol and acetyl-CoA with bovine brain choline acetyltransferase (acetyl-CoA: choline O-acetyltransferase; EC 2.3.1.6). The new product co-chromatographed with authentic diethylaminoethyl acetate on thin layer plates, and its formation was proportional to the duration of incubation and enzyme concentrations. When tested on guinea-pig ileum, diethylaminoethyl acetate was found to be an agonist with an ED50 of 1.3 X 10(-4) M, compared to an ED50 of 2.0 X 10(-7) M for acetylcholine. The contraction of guinea-pig ileum induced by diethylaminoethyl acetate was blocked by atropine. Moreover, diethylaminoethyl acetate induced a secretion of alpha-amylase from isolated pancreatic acini cells; this effect was also blocked by atropine. It is entirely possible that diethylaminoethyl acetate can be a false cholinergic transmitter generated in vivo when drugs such as aprophen or procaine are administered to animals, since either of these drugs can undergo enzymatic hydrolysis to generate diethylaminoethanol. A method for the synthesis of radioactive diethylamino [1,2-14C]ethyl acetate was also described.
D000109:Acetylcholine / Q000031:analogs & derivatives*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005021:Ethylamines / Q000096:biosynthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000096:biosynthesis; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D000516:alpha-Amylases / Q000378:metabolism
D005021:Ethylamines; D018377:Neurotransmitter Agents; D011976:Receptors, Muscarinic; C049455:acetylcaine; D002795:Choline O-Acetyltransferase; D000516:alpha-Amylases; D000109:Acetylcholine