Alteration of metabolism of acetylcholine induced by 2-deoxy-D-glucose in the gastroduodenum of the rat.
2-Deoxy-D-glucose (2-DG) administered intraperitoneally, dose-dependently increased the secretion of gastric acid, and the changes were comparable with those on the activity of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) in the stomach. Double-reciprocal plot analysis of the increased activity of CAT and AChE, induced by 2-DG, showed that the changes were due to the increase of Vmax, with no change in the Km-value for the substrates. The uptake of [3H]choline and subsequent synthesis of [3H]ACh was observed in the forestomach, corpus and antrum of the stomach and in the duodenum. 2-Deoxy-D-glucose significantly increased the uptake of [3H]choline and synthesis of [3H]ACh in every region of the stomach and in the duodenum, in a dose-dependent manner. The increase of secretion of gastric acid, induced by 2-DG paralleled that of uptake of [3H]choline and synthesis of [3H]ACh at an early stage. The conversion of [3H]choline taken up to [3H]ACh was negligibly influenced by 2-DG. Neither the content of ACh and choline, nor the turnover rate of ACh, were changed by administration of 2-DG. 2-Buten-4-olide (2-B4O), which inhibits the activity of the vagus nerve through the central nervous system, prevented 2-DG-induced uptake of [3H]choline and subsequent synthesis of [3H]ACh, as well as the increase in secretion of gastric acid. These results suggest that the uptake of [3H]choline and subsequent synthesis of [3H]ACh are closely related to the neuronal activity of the vagus nerve, and that cholinergic neuronal activity is dependent upon quantitative changes of metabolism of ACh in the gastroduodenum.
Muramatsu
M
M
Department of Pharmacology, Taisho Pharmaceutical Co. Ltd., Ohmiya, Saitama, Japan.
Chaki
S
S
Arai
I
I
Aihara
H
H
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003837:Deoxy Sugars / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects / Q000201:enzymology
D003837:Deoxy Sugars; D007202:Indicators and Reagents; D003847:Deoxyglucose; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline; D000109:Acetylcholine