The gastric mucus layers: constituents and regulation of accumulation.
The mucus layer continuously covering the gastric mucosa consists of a loosely adherent layer that can be easily removed by suction, leaving a firmly adherent mucus layer attached to the epithelium. These two layers exhibit different gastroprotective roles; therefore, individual regulation of thickness and mucin composition were studied. Mucus thickness was measured in vivo with micropipettes in anesthetized mice [isoflurane; C57BL/6, Muc1-/-, inducible nitric oxide synthase (iNOS)-/-, and neuronal NOS (nNOS)-/-] and rats (inactin) after surgical exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa were differently regulated. Luminal administration of PGE(2) increased the thickness of both layers, whereas luminal NO stimulated only firmly adherent mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS-deficient mice had thinner firmly adherent mucus layers and a lower mucus accumulation rate, whereas nNOS did not appear to be involved in mucus secretion. Downregulation of gastric mucus accumulation was observed in Muc1-/- mice. Both the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In conclusion, this study showed that, even though both the two mucus layers covering the gastric mucosa consist of Muc5ac, they are differently regulated by luminal PGE(2) and NO. A new gastroprotective role for iNOS was indicated since iNOS-/- mice had a thinner firmly adherent mucus layer. In addition, a regulatory role of Muc1 was demonstrated since downregulation of gastric mucus accumulation was observed in Muc1-/- mice.
Phillipson
Mia
M
Dept. of Medical Cell Biology, Div. of Integrative Physiology, Biomedical Ctr., Uppsala Univ., P. O. Box 571, SE-751 23 Uppsala, Sweden. mia.phillipson@mcb.uu.se
Johansson
Malin E V
ME
Henriksnäs
Johanna
J
Petersson
Joel
J
Gendler
Sandra J
SJ
Sandler
Stellan
S
Persson
A Erik G
AE
Hansson
Gunnar C
GC
Holm
Lena
L
D000595:Amino Acid Sequence; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000502:physiology*; D009093:Mucus / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
C506177:MUC1 protein, rat; D018396:Mucin-1; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D015232:Dinoprostone; D007213:Indomethacin