Transport of dimethylamine, a precursor of nitrosodimethylamine, into stomach of ferret and dog

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Abstract
Dimethylamine is important because it is a precursor of nitrosodimethylamine, a suspected carcinogen in man. Significant quantitites of dimethylamine and nitrite are found in gastric fluid, and conditions in the stomach are favorable for nitrosodimethylamine formation. Little is known about the origins of dimethylamine in gastric fluid. Studies were performed to determine whether dimethylamine can be transported from blood to gastric fluid. There was no diurnal variation of the dimethylamine content in gastric fluid or blood from untreated dogs. We administered 50 mg/kg dimethylamine i.v. to dogs and ferrets and collected blood and gastric fluid samples at timed intervals. In both species we observed similar kinetics of dimethylamine distribution into biologic fluids. Dimethylamine concentrations in blood and gastric fluid rose rapidly during the first minutes after treatment. Blood dimethylamine concentrations peaked within 30 min after the dose (rising from 10 to 430 nmol/ml in the dogs, and from 30 to 430 nmol/ml in the ferrets). Dimethylamine concentrations in blood slowly decreased thereafter. Gastric fluid dimethylamine concentrations continued to rise for 3 h after the dose (from 40 to 540 nmol/ml in the dogs, and from 40 to 1056 nmol/ml in the ferrets). Gastric fluid dimethylamine remained elevated for more than 5 h. Between 1 h and 5 h after treatment, gastric fluid dimethylamine concentrations were significantly higher than blood dimethylamine concentrations (by >2.5 x). In gastric fluid from control animals, dimethylamine concentration exceeded monomethylamine concentration, which in turn was higher than trimethylamine concentration. Administration of dimethylamine transiently increased gastric fluid monomethylamine content, but had little effect upon trimethylamine concentration. These data demonstrate that dimethylamine is efficiently transported from blood into gastric fluid.