[Effect of indomethacin on the secretion of pepsinogen in isolated human cells in vitro].
The effects of indomethacin on pepsinogen secretion were studied in isolated human peptic cells prepared from endoscopically obtained biopsies after collagenase digestion, mechanical disruption and percoll gradient centrifugation. Low concentrations of indomethacin (10(-8)-10(-10) M) stimulated basal pepsinogen secretion. Higher doses of indomethacin (10(-5)-10(-6) M) potentiated histamine (10(-4) M) and db-cAMP (10(-4) M)-stimulated pepsinogen secretion without affecting acetylcholine (10(-6) M) and CCK-8-stimulated pepsinogen secretion or cell vitality. Increase of pepsinogen secretion was dependent on extracellular calcium because potentiation was abolished by calcium depletion of the medium. We conclude that indomethacin potentiates basal and secretagogue-stimulated pepsinogen secretion by dispersed human peptic cells and this might be an additional mechanism of NSAID-induced gastric injury. This potentiation effect is regulated by calcium and independent of endogenous prostaglandin inhibition.
Serrano Aulló
M T
MT
Servicio de Aparato Digestivo, Hospital Clínico Universitario. Zaragoza.
Nerín de la Puerta
J M
JM
Lanas Arbeloa
A I
AI
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology; D003470:Culture Media; D000242:Cyclic AMP / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010435:Pepsinogens / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003470:Culture Media; D010435:Pepsinogens; D006632:Histamine; D002766:Cholecystokinin; D000242:Cyclic AMP; D000109:Acetylcholine; D007213:Indomethacin