cyclic-gmp and Celiac-Disease

The activity of nitric oxide synthase (NOS) was assayed in enterocytes isolated from human duodenal biopsies to determine its role in celiac disease. Patients were categorized into groups with irritable bowel syndrome, iron-deficiency anemia, B(12)/folate deficiency, and treated and untreated celiac disease. Enterocytes isolated from all groups showed 1400W-inhibitable Ca2+-independent NOS activity with a pH level and temperature optimum of 9.4 and 37 degrees C, respectively. Western blotting showed that enterocytes expressed the inducible NOS protein and proteins with nitrated tyrosine residues, the latter being indicative of nitric oxide-driven peroxynitrite and/or free-radical damage. Endothelial NOS was seen only in the lamina propria. Patients with celiac disease had higher NOS activity than other patient groups. Treatment of the condition led to a fall in activity. Enzyme-linked immunosorbent assay demonstrated cGMP production by the enterocyte fraction, but cGMP levels did not correlate with NOS activity. These results suggest that inducible NOS is constitutively expressed in human duodenal enterocytes, is increased in patients with untreated celiac disease, and is partially corrected when such patients are treated. We found no evidence to support a role for nitric oxide in the formation of cGMP within the small intestine. Furthermore, we were unable to demonstrate a role for peroxynitrite/free radical damage in the pathophysiology of celiac disease.

Topics: Blotting, Western; Celiac Disease; Cyclic GMP; Duodenum; Enterocytes; Humans; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Peroxynitrous Acid

This study measured the values of cyclic nucleotides and adenylate and guanylate cyclase activities in duodenal mucosa homogenates to verify if they played a part in coeliac disease. Nine controls, 13 patients who did not receive treatment and nine patients who received treatment were studied. Cyclase activity assays were performed under basal conditions and in the presence of gliadin derived peptides. Duodenal mucosa cyclic nucleotide values and adenylate cyclase activity were significantly higher in patients who did not receive treatment than in those who did and in controls, whereas guanylate cyclase activity was similar in all groups. Gliadin derived peptides did not affect guanylate cyclase activity, but significantly increased adenylate cyclase activity in homogenates from patients who did not receive treatment. As extracellular cyclic nucleotide concentrations could reflect changes in their intracellular metabolism, plasma and urine cyclic nucleotide values were also measured in 25 controls and in 55 patients studied at different stages of their disease. Extracellular cyclic nucleotides were considerably high in patients who were not healed and became normal after about one year of treatment. These data suggest that cyclic nucleotides may participate in the pathophysiological processes of coeliac disease.

Topics: Adenylyl Cyclases; Adult; Aged; Celiac Disease; Cyclic AMP; Cyclic GMP; Duodenum; Extracellular Space; Female; Guanylate Cyclase; Humans; Intestinal Mucosa; Male; Middle Aged; Nucleotides, Cyclic