Role of endogenous nitric oxide in duodenal bicarbonate response induced by mucosal acidification in rats: Interaction with prostaglandins

Abstract

Background & Aim. The circulating peptide leptin produced by the fat cells, acts on central receptors to control food intake and body weight homeostasis. Contrary to initial reports, leptin expression has also been detected in the human placenta, the muscles and recently rat gastric chief cells. Here we investigate the possible presence of leptin and leptin receptor in human stomach. Methods. Immunohistochemistry, reverse transcriptase (RT-PCR) and western blot analysis on biopsy samples from 24 normal individuals was used to investigate leptin and leptin receptor expressions. These individuals were randomly selected from the files of our Gastroenterology Department. They included 15 healthy volunteers and 9 patients with non-ulcer dyspepsia (n=24) who gave informed consent for upper endoscopy and gastric secretory tests. Secretory studies upon pentagastrin (6J,Lg/kg/hr) or secretin (3Ul/kg.hr) infusions, available for 22 subjects (mean age 46.7::':: 3.lyears; range 15-67,9 women, l3 men) were analyzed. At the time of study, all had normal endoscopy and normal gastric mucosa on histological examination. Plasma, gastric juice and fundic mucosa leptin were determined by radioimmunoassay. Results. In fundic biopsies from normal individuals, immunoreactive leptin cells were found in the lower half of the fundic glands at the site of chief cells. mRNA encoding ob-protein was detected in the corpus of human stomach. The amount of fundic content of leptin was 10.4 ::':: 3.7 ng leptin/g mucosa as determined by radioimmunoassay. Intravenous infusions of pentagastrin or secretin caused an increase in circulating leptin levels and leptin release into the gastric juice from 24.5 ::'::.3.5 in basal condition to 109 ::':: 26 ng/h under pentagastrin and 1556 ::':: 107 ng/hr under secretin. Gel filtration of leptin incubated with stimulated gastric juice at pH 2 showed an only limited degradation of this peptide. Immunohistochemistry and immunoblotting detected leptin receptor protein and mRNA encoding Ob-RL in the corpus and the antrum. Conclusion. These data provide the first evidence for the presence of leptin and leptin receptors in human stomach. We suggest that gastric epithelial cells be direct targets of leptin. However, the physiological and/or pathophysiological meanings of these findings remain so far unknown.