Different effects of intraperitoneal or subcutaneous administration of H2-antagonists on pancreatic response to chronic administration of caerulein in rats.

This study deals with the effect of H2-receptor antagonists on pancreatic response to chronic administration of caerulein. Caerulein was administered alone or combined with cimetidine, ranitidine or famotidine twice a day in various regimes. At the end of treatment, pure pancreatic juice was collected after hormonal stimulation. Then, the rats were killed, and growth and composition of the pancreatic tissue were determined. Caerulein increased pancreatic weight and enzyme content as well as volume and enzyme activity of pancreatic juice. When given alone the three H2-receptor antagonists were totally ineffective. Both ranitidine and famotidine, but not cimetidine, significantly reduced pancreatic response to chronic administration of caerulein only when given intraperitoneally together with caerulein. On the contrary, separate applications of caerulein and ranitidine (or famotidine) did not influence caerulein-stimulated pancreatic growth or enzyme secretion. Moreover, in rats treated both intraperitoneally and subcutaneously with caerulein, the H2-antagonists reduced the pancreatic response only partially and in proportion to the intraperitoneal dose of caerulein. The responsiveness of pancreatic tissue to subcutaneous caerulein was not modified. The results suggest that H2-receptor antagonists induce (1) impaired uptake of caerulein when given together with peptide, but (2) have no specific inhibitory effect on pancreatic response to caerulein.