Systemically administered trefoil factors are secreted into the gastric lumen and increase the viscosity of gastric contents.
OBJECTIVE
Trefoil factors (TFFs) secreted by mucus-producing cells are essential for the defence of the gastrointestinal mucosa. TFFs probably influence the viscoelastic properties of mucus, but this has not been demonstrated in vivo. We therefore studied the gastric secretion of systemically administered TFF2 and TFF3, and their influence on the viscosity of the secretions.


METHODS
Mice and rats under general anaesthesia were injected intravenously with human (h) TFF2, hTFF3 (5 mg kg(-1) to mice and 25 mg kg(-1) to rats), murine (m) (125)I-TFF3, or (125)I-hTFF3 (300,000 cpm, mice only). The appearance of TFFs in the gastric mucosa and luminal secretions was analysed by autoradiography, gamma-counting, and ELISA, and the viscosity by rheometry.


RESULTS
(125)I-mTFF3 and (125)I-hTFF3 were taken up by secretory cells of the gastrointestinal tract and detected at the gastric mucosal surface 15 min after injection. Stressing the stomach by carbachol (3.5 microg kg(-1)) and pyloric ligation significantly increased the uptake. Injected hTFF2, hTFF3, and mTFF3 were retrieved from the gastric contents after 4 h. In rats, an approximately seven-fold increase in the viscosity was detected after injection of TFF2 compared to the controls, whereas TFF3 did not increase the viscosity. In mice, TFF2 increased the viscosity approximately 4-fold.


CONCLUSIONS
These data indicate that systemically administered TFFs are transferred to the gastric lumen in a biologically active form.
Kjellev
S
S
Pharmacology Research 4, Novo Nordisk a/s, Maaloev, Denmark. skje@novonordisk.com
Nexø
E
E
Thim
L
L
Poulsen
S S
SS
D000818:Animals; D001345:Autoradiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D005766:Gastrointestinal Contents / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D000071164:Trefoil Factor-2; D014783:Viscosity / Q000187:drug effects
D010455:Peptides; C000604007:TFF2 protein, human; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2