Synthetic 13C-dipeptide breath test for the rapid assessment of pancreatic exocrine insufficiency in rats.
OBJECTIVE
(13)C-breath tests have been investigated in order to assess pancreatic exocrine function using various (13)C-compounds, but they have not been accepted for routine clinical use. One of the barriers to their acceptance is that these tests are time-consuming and require up to several hours for breath collection. The purpose of this study was to design a novel (13)C-compound that would make a rapid (13)C-breath test for assessing exocrine pancreatic function possible.


METHODS
N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was synthesized, and the characteristics of its cleavage in duodenal juice and in the duodenum of rats were examined. Thereafter, a (13)C-breath test was carried out in which N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was given orally to pancreatic exocrine-insufficient and normal control rats.


RESULTS
N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was readily cleaved and liberated 1-(13)C-L-alanine in the duodenal juice. Carboxypeptidase was a major contributor to the cleavage. When N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was injected into the duodenum and orally administered to the rats, the (13)C atom% of CO(2) in breath increased rapidly. This indicated that N-benzoyl-L-tyrosyl-1-(13)C-L-alanine in the duodenum liberated (13)C-Ala on cleavage. (13)C-Ala is absorbed and metabolized to liberate (13)CO(2), which is exhaled. It was shown that the Delta(13)CO(2) ( per thousand) in the N-benzoyl-L-tyrosyl-1-(13)C-L-alanine breath test in the pancreatic exocrine-insufficient rats, in whom the absorption and metabolism of (13)C-Ala was unimpaired, was significantly lower than that in the control rats.


CONCLUSIONS
The rate of increase in the Delta(13)CO(2) ( per thousand) in the N-benzoyl-L-tyrosyl-1-(13)C-L-alanine breath test is expected to be proportional to the rate of N-benzoyl-L-tyrosyl-1-(13)C-L-alanine cleavage by pancreatic proteases in the duodenum. We propose the N-benzoyl-L-tyrosyl-1-(13)C-L-alanine breath test as a rapid test for assessing pancreatic exocrine function.
Kohno
Tadashi
T
Fundamental Technology Department, Tokyo Gas Co. Ltd., Tokyo, Japan.
Ito
Asuka
A
Hosoi
Isaburo
I
Hirayama
Junko
J
Shibata
Kunihiko
K
D000818:Animals; D001944:Breath Tests / Q000379:methods*; D002247:Carbon Isotopes; D004151:Dipeptides; D010188:Exocrine Pancreatic Insufficiency / Q000175:diagnosis*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002247:Carbon Isotopes; D004151:Dipeptides