Sequential expression of adrenomedullin and its receptor during gastric ulcer healing in rats

Adrenomedullin (AM) is a potent vasodilatory peptide. While its growth-regulating action in some cultured cells has been recognized, expression of AM and its receptor during gastric ulcer healing has not been explored. Specimens of gastric walls from control rats or gastric ulcers were obtained at 1, 3, 7, and 14 days after gastric ulcer induction. AM and its receptor mRNAs expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. By RT-PCR, AM mRNA was increased by 167% at three days, while AM receptor mRNA was increased by 234% at seven days (both P < 0.05). By in situ hybridization, AM and AM receptor mRNAs were increased at ulcer margin from three days after ulcer induction. By immunohistochemistry, AM was increased in the ulcer margin at three and seven days. In separate in vitro studies using a rat gastric epithelial (RGM1) cell line, AM treatment significantly increased transforming growth factor-alpha mRNA expression and cell proliferation.