Cholecystokinin-B/gastrin receptors enhance wound healing in the rat gastric mucosa

Although physiological functions of the CCK-B/gastrin receptor are well exp lored, little is known about its role during healing. Here, we evaluated th e role of this receptor in the rat oxyntic mucosa following the introductio n of a cryoulcer. In this model, we located and quantified CCK-B/gastrin re ceptors by reverse transcriptase PCR and receptor autoradiography. Rats wit h cryoulcers were treated with placebo, omeprazole, the CCK-B/gastrin recep tor antagonist YF-476, omeprazole plus YF-476, gastrin-17, and gastrin 17 p lus YF-476. During wound healing, CCK-B/gastrin receptors were specifically expressed and localized to the regenerative mucosal ulcer margin. This hig h expression was limited in time, and the pattern of expression of CCK-B/ga strin receptors correlated closely with the proliferative activity of the r egenerative 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 completel y reversed by cotherapy with YF-476. These in vivo and vitro data suggest t hat CCK-B/gastrin receptors in regenerative rat gastric oxyntic mucosa enha nce trophic effects during wound healing.