On the mode of action of caerulein in evoking enzyme release of the rat pancreas

Abstract

1. The actions of caerulein and cholecystokinin-pancreozymin (CCK-Pz) on the secretion of pancreatic protein and amylase, were compared in the in situ rat pancreas or the isolated and perfused rat pancreas.
2. Caerulein displayed a potent stimulant action on the release of pancreatic enzymes. The threshold dose in situ was 3ng/rat by rapid intravenous injection. In proportion to the logarithmic increase in dose up to 96ng/rat, the secretory response was enhanced linearly. However, further increasing the dose, lesser release rather than greater release was evoked. In the isolated and perfused pancreas, the threshold concentration of caerulein was estimated to be 0.01ng/ml. In proportion to the logarithmic increase in dose up to 0.1ng/ml, the amylase output was increased linearly. Further increase in dose evoked lesser output.
Thus, the secretory activity of 20-24ng of caerulein is equivalent to that of 1 Crick, Harper and Raper unit of CCK-Pz.
3. The effect of caerulein was partially inhibited after administration of atropine (1.5 mg/kg b. w.), but the effect of CCK-Pz was not altered after atropinization in the in situ rat pancreas.
4. The effect of both caerulein and CCK-Pz on the protein release was greater when the drugs were injected into the femoral veins than when injected into the portal veins. These observations indicate that both caerulein and CCK-Pz seem to be partially inactivated by the liver.
5. The effect of caerulein on the release of pancreatic amylase depended on Ca²⁺-in the medium perfusing the blood vessels of the pancreas.
6. Observation of the surface of acinar lumen by scanning electron microscopy supported the views that caerulein induces the extrusion of zymogen granules at the luminar surface of the pancreatic acinar cells by the process of Ca²⁺-dependent exocytosis.
7. Caerulein and CCK-Pz are shown to have a similar effect on the release of pancreatic enzymes except that caerulein seems to act on the pancreas partially by activating the vagal nerve.