Nitecapone effect on the synthesis and secretion of gastric sulfomucin.
1. The effect of a new antiulcer agent, nitecapone, on the synthesis and secretion of sulfomucin in gastric mucosa was investigated using mucosal segments incubated in the presence of [3H]proline, [3H]glucosamine and [35S]sulfate. 2. The drug, while showing no discernible effect on the apomucin synthesis, evoked a dose-dependent increase in mucin glycosylation and sulfation, which at 225 microM nitecapone, attained its maximum of 1.8 and 2.2-fold stimulation, respectively. 3. The analysis of mucin secretory responses revealed that nitecapone caused a concentration-dependent enhancement in sulfomucin secretion attaining maximum increase of 1.5-fold at 150 microM nitecapone. 4. The stimulatory effect of nitecapone on sulfomucin secretion was accompanied by 1.4-fold increase in mucosal cAMP level, and showed sensitivity to protein kinase A inhibitors, thus pointing towards the involvement of protein kinase A in mediation of gastric sulfomucin secretory responses to nitecapone. 5. The ability of nitecapone to enhance sulfomucin synthesis and secretion could be of importance to the gastroprotective action of this agent.
Research Center, University of Medicine and Dentistry of New Jersey, Newark 07103-2400.
B L
BL
Slomiany
Y H
YH
Liau
R A
RA
Lopez
A
A
Slomiany
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005944:Glucosamine / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis; D066298:In Vitro Techniques; D009077:Mucins / Q000096:biosynthesis* / Q000378:metabolism; D010422:Pentanones / Q000494:pharmacology*; D011392:Proline / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D051381:Rats; D013462:Sulfur Radioisotopes
D000897:Anti-Ulcer Agents; D002396:Catechols; D006023:Glycoproteins; D009077:Mucins; D010422:Pentanones; D047428:Protein Kinase Inhibitors; D013462:Sulfur Radioisotopes; C012564:sulfomucin; C057364:nitecapone; D011392:Proline; D000242:Cyclic AMP; D005944:Glucosamine