Expression of functional neurokinin-1 receptors in regenerative glands during gastric wound healing in rodents.
OBJECTIVE
Although functions of the neurokinin-1 receptor have been well explored in neurogenic inflammation and immunoinflammatory responses, little is known about neurokinin-1 receptors during gastric wound healing. The aim of this study was to assess whether neurokinin-1 receptors play a role in gastric wound healing.


METHODS
In vitro neurokinin-1 receptor autoradiography and immunohistochemistry were performed to identify, locate, and quantify neurokinin-1 receptors during wound healing in rodents with cryoulcers in the gastric corpus and antrum. Moreover, to assess the functionality of these receptors, the effect of the neurokinin-1 receptor antagonist NKP608 on gastric wound healing was quantified in vivo in wild-type and cyclooxygenase-2(-/-) mice.


RESULTS
Regenerative glands of the mucosal ulcer margin of rat cryoulcers of the gastric corpus showed strong expression of neurokinin-1 receptors in binding studies between days 3 and 22, with little expression on days 29-84. In addition, strong immunoreactivity for neurokinin-1 receptors was detected on the cell membrane of these regenerative glands. Expression of neurokinin-1 receptors in regenerative glands was confirmed in the rat antrum and the mouse gastric corpus. Moreover, in vivo functional tests during gastric ulcer healing showed that cell proliferation in the regenerative epithelia of the ulcer margin was significantly decreased by NKP608 compared with placebo; furthermore, gastric ulcer healing was significantly delayed by NKP608 both in wild-type and cyclooxygenase-2(-/-) mice.


CONCLUSIONS
This report shows the time-limited overexpression of neurokinin-1 receptors in the mucosal repair tissue of the corpus and antrum. Our in vitro and in vivo data suggest that neurokinin-1 receptors are involved in gastric wound healing.
Schmassmann
Adrian
A
Gastrointestinal Unit, University Hospital, University of Berne, Switzerland.
Waser
Bea
B
Flogerzi
Beatrice
B
Reubi
Jean Claude
JC
D000818:Animals; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D051546:Cyclooxygenase 2; D005260:Female; D005615:Freezing; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012038:Regeneration; D013276:Stomach Ulcer / Q000209:etiology / Q000503:physiopathology*; D013997:Time Factors; D014018:Tissue Distribution; D014945:Wound Healing
D007527:Isoenzymes; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011804:Quinolines; D018040:Receptors, Neurokinin-1; C414491:quinoline-4-carboxylic acid (1-(3,5-bis-trifluoromethylbenzoyl)-2-(4-chlorobenzyl)piperidin-4-yl)amide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases