CGRP modulates mucin synthesis in surface mucus cells of rat gastric oxyntic mucosa.
We examined the effects of the calcitonin gene-related peptide (CGRP), including the possible participation of nitric oxide (NO), on mucin biosynthesis in the surface epithelium and remaining deep mucosa as well as the entire mucosa and compared the distribution of CGRP and NO synthase (NOS) using a combination of double immunofluorescence labeling and multiple dye filter. Pieces of tissue obtained from the corpus and antrum were incubated in a medium containing [(3)H]glucosamine and CGRP, with or without the NOS inhibitor. CGRP dose-dependently enhanced [(3)H]glucosamine incorporation into the corpus mucin but had no effect on antral mucin biosynthesis. The CGRP receptor antagonist, CGRP-(8-37), prevented the increase in (3)H-labeled corpus mucin. This stimulation of corpus mucin synthesis disappeared after removal of the surface mucus cell layer. CGRP activated the mucin biosynthesis in the surface mucus cells. In the full-thickness corpus mucosa, CGRP-induced activation was completely blocked by the NOS inhibitor. CGRP-immunoreactive fibers were intertwined within the surface mucus cell layer with type I NOS immunoreactivity. These results show that CGRP-stimulated mucin biosynthesis mediated by NO is limited to surface mucus cells of the rat gastric oxyntic mucosa.
Ichikawa
T
T
Department of Biochemistry, Kitasato University School of Medicine, Japan. t.ichika@kitasto-u.ac.jp
Ishihara
K
K
Kusakabe
T
T
Hiruma
H
H
Kawakami
T
T
Hotta
K
K
D000818:Animals; D000906:Antibodies; D001565:Benzoates / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D005944:Glucosamine / Q000493:pharmacokinetics; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009077:Mucins / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
D000906:Antibodies; D001565:Benzoates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009077:Mucins; D010446:Peptide Fragments; D014316:Tritium; C058636:calcitonin gene-related peptide (8-37); C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide; D005944:Glucosamine