Effect of ebrotidine on the synthesis and secretion of gastric sulfomucin.
1. The effect of a new antiulcer agent, ebrotidine, on the synthesis and secretion of sulfomucin in gastric mucosa was investigated. Rat gastric mucosal segments were incubated in DMEM containing [3H]proline, [3H]glucosamine and [35S]Na2SO4 as markers for mucin synthesis, glycosylation and sulfation, in the presence of 0-150 microM ebrotidine. 2. The drug, while showing no discernible effect on the apomucin synthesis, evoked a dose-dependent increase in mucin glycosylation and sulfation, which at 100 microM ebrotidine, attained its maximum of 2.4 and 2.7-fold stimulation, respectively. 3. The analysis of mucin secretory responses revealed that ebrotidine caused a concentration-dependent enhancement in sulfomucin secretion which attained its maximum increase of 3.3-fold at 100-120 microM ebrotidine. Furthermore, the sulfomucin elaborated in the presence of ebrotidine exhibited a higher content of a large molecular-weight mucus glycoprotein form, the assembly of which is intimately associated with the sulfation event. 4. The results suggest that the ability of ebrotidine to enhance gastric sulfomucin synthesis and secretion may play an important role in the gastroprotective mechanism of action of this agent.
Slomiany
B L
BL
Research Center, University of Medicine and Dentistry of New Jersey, Newark 07103.
Lopez
R A
RA
Liau
Y H
YH
Slomiany
A
A
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005944:Glucosamine / Q000378:metabolism; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism; D066298:In Vitro Techniques; D009077:Mucins / Q000096:biosynthesis* / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D051381:Rats; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013844:Thiazoles / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D001557:Benzenesulfonates; D006023:Glycoproteins; D009077:Mucins; D013431:Sulfates; D013462:Sulfur Radioisotopes; D013844:Thiazoles; C012564:sulfomucin; D011392:Proline; D005944:Glucosamine; C075156:ebrotidine