Apoptosis in rat gastric antrum: Evidence that regulation by food intake depends on nitric oxide synthase

The turnover of the epithelium of the gastrointestinal tract is regulated b y a balance between cell multiplication and cell loss. We examined the effe cts of starvation on apoptosis in endocrine and other epithelial cells of r at antropyloric mucosa. Apoptosis was determined by the TUNEL reaction comb ined with immunocytochemical staining for gastrin and somatostatin. Apoptot ic cell morphology was determined by bisbenzimide staining for DNA. Both ga strin and somatostatin cells showed a significantly lower apoptotic index t han the general epithelium. This agrees with the longer turnover kinetics o f gastric endocrine cells. On starvation, the apoptotic index of the genera l epithelium and of the gastrin but not of the somatostatin, cells increase d significantly. This was prevented by the nitric oxide synthase (NOS) inhi bitor L-NAME but not by its inactive stereoisomer D-NAME. Immunoreactive ne uronal NOS was present in somatostatin cells, in nonendocrine cells predomi nating in the surface and pit epithelium, and in rare nerve fibers. Endothe lial cell NOS was present in vessels, whereas the inducible isoform was bar ely detectable. Thus, endogenous NOS isoforms participate in regulating ant ropyloric epithelial apoptosis during starvation. The close paracrine relat ion between somatostatin cells and gastrin cells suggests that the former r egulates apoptosis of the latter through release of NO.