Changes in zymogen granule membrane and pancreatic juice after supramaximal stimulation with caerulein in the rat

Pancreatic exocrine secretion was stimulated supramaximally with an intravenous infusion of 10 micrograms/kg of body weight of caerulein for 10 min in four rats. Two animals were killed immediately, and two animals 120 min after the cessation of the caerulein infusion. In specimens fixed immediately after the caerulein infusion, there were irregular electron lucent structures that resembled zymogen granules and were associated with bristle-coated membranes, coated pits and coated vesicles. Two hours after the caerulein infusion there were large vacuoles that contained amorphous or membranous material and cell organelles in acinar cells. The HPLC-analysis of pancreatic juice revealed two new peaks after caerulein injection. It was concluded that supramaximal caerulein stimulation prevents normal maturation and discharge of zymogen granules leading to altered membrane recycling of secretory granules in acinar cells and to the appearance of abnormal secretory products in pancreatic juice. The novel ultrastructural findings of this study, the bristle-coated membranes and the coated pits in the membrane of dilated zymogen granules, may be related to the exceedingly high dose of caerulein administered.