AJP - Gastrointestinal and Liver Physiology, Vol 254, Issue 6 849-G855, Copyright © 1988 by American Physiological Society
Effects of leukotriene C4 on pancreatic secretion and circulation in dogs
S. J. Konturek, W. Pawlik, K. Czarnobilski, P. Gustaw, J. Jaworek, G. Beck and H. Jendralla
Institute of Physiology, Academy of Medicine, Krakow, Poland.
In the present study the effects of leukotriene C4 (LTC4) on exocrine
pancreatic secretion and pancreatic blood flow were determined. LTC4 given
intravenously in various doses ranging from 0.35 to 2.8 nmol.kg-1.h-1 in
conscious dogs caused a dose-dependent inhibition of pancreatic HCO-3 and
protein responses to exogenous hormones such as secretin, cholecystokinin
octapeptide (CCK-8), and bombesin and to endogenous stimulants including
meat feeding and duodenal perfusion with oleate. In tests with pancreatic
secretion induced by secretin plus CCK, maximal inhibition by LTC4 occurred
at a dose of 1.4 nmol.kg-1.h-1 and reached approximately 70% of the control
value for HCO-3 output and 45% for protein output. In tests with separate
secretin- or CCK-induced secretion, maximal inhibition occurred at a dose
of 1.4 nmol.kg-1.h-1 and reached 38 and 66% of the control HCO-3 and
protein secretion, respectively. The same dose of LTC4 reduced the
postprandial HCO-3 secretion by approximately 80% and protein output by
approximately 70%. After administration of indomethacin, the pancreatic
secretion declined, but the inhibitory effects of LTC4 remained unchanged.
Pancreatic tissue generated two to three times more LTC4 than the
gastrointestinal mucosa, and indomethacin caused further increase in this
generation, suggesting that LTC4 may contribute to indomethacin-induced
pancreatic inhibition. (ABSTRACT TRUNCATED AT 250 WORDS)
