Uptake of extracellular, dietary putrescine is an important regulatory mechanism of intracellular polyamine metabolism during camostate-induced pancreatic growth in rats

Abstract

Aim of the present study was to evaluate the role of cellular uptake of dietary [3H]putrescine for the regulation of pancreatic, hepatic, and small intestinal polyamine metabolism during normal and camostate-induced pancreatic growth in rats in vivo. Initially dose-response and time-course studies of [3H]putrescine uptake were performed. Male Wistar rats were either treated with the synthetic trypsin inhibitor camostate (200 mg/kg body wt orally twice daily), camostate plus the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO) (2% in drinking water plus 3 x 300 mg/kg body wt intraperitoneally during daytime) or saline as controls. After 4, 8, 12, 24, 36, 48, or 120 hr, five to seven animals per group were killed, respectively. Orally fed [3H]putrescine (10 nmol/kg body wt. 2 hr prior to death) is rapidly taken up and further metabolized to spermidine in normal growing pancreas, liver, and small intestine. Feeding of camostate significantly enhanced dietary [3H]putrescine uptake, while simultaneous inhibition of de novo synthesis of intracellular polyamines by DFMO resulted in a highly significant further increase in cellular uptake of orally fed [3H]putrescine, which is immediately metabolized to spermidine. The present in vivo data confirm the important role of dietary putrescine uptake for the maintenance of intracellular polyamine pool in normal and stimulated pancreatic growth. Furthermore, dietary putrescine uptake is an important regulatory mechanism to maintain the normal and growth-stimulated cellular polyamine pool in the pancreas after potent simultaneous inhibition of intracellular de novo polyamine synthesis.