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Cholecystokinin-B/gastrin receptors enhance wound healing in the rat gastric mucosa
Adrian Schmassmann, Jean Claude Reubi
Adrian Schmassmann, Jean Claude Reubi
Published October 15, 2000
Citation Information: J Clin Invest. 2000;106(8):1021-1029. https://doi.org/10.1172/JCI8115.
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Article

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

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Abstract

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.

Authors

Adrian Schmassmann, Jean Claude Reubi

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Figure 1

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(a and b) Normal oxyntic mucosa from control rats. (c–e) Ulcerated tissu...
(a and b) Normal oxyntic mucosa from control rats. (c–e) Ulcerated tissue 8 days after ulcer induction showing normal mucosa (muc), regenerative mucosa in the repair zone (arrowheads), and an ulcer crater (ulcer). (a, c, d) In situ hybridization for pepsinogen mRNA (black) and immunostaining for the H+,K+-ATPase protein (red); (b and e) BrdU immunostaining. In the normal mucosa (a), chief cells (black) are located in the basal mucosa; in contrast, parietal cells (red) are located throughout the mucosa. In the regenerative glands (c and d), no signals for pepsinogen mRNA and H+,K+-ATPase protein were detected. Whereas BrdU-labeled cells were confined to the neck region in the normal mucosa (b), abundant BrdU labeling was observed in the basal part of regenerative glands close to the ulcer crater (e). Bar, 100 μm in a, b, d, e; bar, 500 μm in c.

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