Changes in the structure of rat mucous glycoprotein and prostaglandin cytoprotection

Using a mucolytic agent, N-acetyl-L-cysteine (NAC), the structure of rat gastric mucous glycoprotein (GP) and its participation in prostaglandin cytoprotection were studied. Treatment of the undegraded native mucous GP with 20% NAC resulted in a marked reduction in molecular weight as obtained in the case of treatment with 0.5 M beta-mercaptoethanol. The amount of GP remaining in the gastric tissue, including the mucous layer after 3 h-incubation was defined as an indication of the mucous adhesiveness to the gastric mucosal surface. The adhesiveness was markedly decreased by the in vitro or in vivo treatment with NAC. The cytoprotective effect of prostaglandin E2 was significantly reduced by pretreatment with NAC. Elution profiles of mucous GP on Sepharose CL-2B showed a good correlation between decrease in the amount of the undegraded native mucous GP and the severity of gastric damage. In addition, the collapse of the native mucous GP into its subunits resulted in a decrease in the adhesiveness. These observations suggest that the maintenance of the native mucous GP is an essential factor for prostaglandin cytoprotection.