<b>SECRETIN PREVENTS HYPOREACTIVE AND MORPHOLOGICAL RESPONSES OF RAT PANCREATIC ACINAR CELLS TO STIMULATION WITH SUPRAOPTIMAL CONCENTRATION OF </b><b>CHOLECYSTOKININ-OCTAPEPTIDE </b>

Abstract

Secretagogues at concentrations greater than those required for maximum secretory responses (as measured in pancreatic protein output and juice flow) induce submaximal responses. In the isolated perfused rat pancreas, a high concentration of cholecystokinin-octapeptide (1 or 100 nM CCK-8) produced secretory responses significantly smaller than maximal responses. This hyporeactive response to supraoptimal stimulation coincided with a profound alteration in acinar cell morphology asfollows: 1) disappearance of microvilli from the luminal acinar cell surface, 2) appearance of cytoplasmic ‘lakes’ of zymogen material bounded by a membrane and located among normal looking mitochondria and cisternae of granular endoplasmic reticulum, and 3) destruction of cytoplasmic microfilaments detected immunohistochemically by an anti-actin antibody. In contrast to these alterations, stimulation with 1 nM CCK-8 in combination with 100 pM secretin: 1) preserved the acinar cell ultrastructure and microfilaments so that they resembled those in the control pancreas (without stimulation) and pancreas stimulated with lower doses of CCK-8; and 2) regained the maximal secretory responses equivalent to those with the optimal CCK-8 concentration of 100 pM. It is concluded, therefore, that: 1) secretin prevents the hyporeactive and morphological alteration of pancreatic acinar cell induced by supraoptimal stimulation with CCK-8; and 2) the alterations may be mediated by microfilaments containing immunoreactive actin. These observations provide an experimental basis for the administration of secretin to prevent the development of pancreatitis induced by a supraoptimal plasma CCK level.