Cholecystokinin-B/gastrin receptors enhance wound healing in the rat gastric mucosa.
Although physiological functions of the CCK-B/gastrin receptor are well explored, little is known about its role during healing. Here, we evaluated the role of this receptor in the rat oxyntic mucosa following the introduction of a cryoulcer. In this model, we located and quantified CCK-B/gastrin receptors by reverse transcriptase PCR and receptor autoradiography. Rats with cryoulcers were treated with placebo, omeprazole, the CCK-B/gastrin receptor antagonist YF-476, omeprazole plus YF-476, gastrin-17, and gastrin 17 plus YF-476. During wound healing, CCK-B/gastrin receptors were specifically expressed and localized to the regenerative mucosal ulcer margin. This high expression was limited in time, and the pattern of expression of CCK-B/gastrin receptors correlated closely with the proliferative activity of the regenerative mucosa. Functionally, omeprazole and gastrin-17 caused profound hypergastrinemia, increased cell proliferation in the mucosal ulcer margin and accelerated the late ulcer healing phase. These effects were completely reversed by cotherapy with YF-476. These in vivo and vitro data suggest that CCK-B/gastrin receptors in regenerative rat gastric oxyntic mucosa enhance trophic effects during wound healing.
Schmassmann
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Gastrointestinal Unit, Inselspital, University Hospital, University of Berne, Berne, Switzerland. adrian.schmassmann@kss.gsd.lu.ch
Reubi
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JC
D000818:Animals; D001570:Benzodiazepinones / Q000627:therapeutic use; D005260:Female; D005615:Freezing; D005753:Gastric Mucosa / Q000293:injuries / Q000502:physiology*; D005755:Gastrins / Q000627:therapeutic use; D009853:Omeprazole / Q000627:therapeutic use; D010295:Parietal Cells, Gastric / Q000187:drug effects; D010671:Phenylurea Compounds / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012038:Regeneration; D013276:Stomach Ulcer / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C013550:gastrin 17; C104428:YF 476; D009853:Omeprazole