The effect of extracellular calcium deprivation on amylase secretion and 45Ca efflux from rat pancreas.

1. The role of extracellular Ca(2+) in pancreatic enzyme secretion and (45)Ca efflux evoked by acetylcholine (ACh) and caerulein has been assessed in the incubated, uncinate pancreas of young rats.2. In a medium containing 2.5 x 10(-3)m-Ca(2+), the maximal rates of amylase secretion evoked by optimal doses of each secretagogue were similar. However, the time courses of amylase release during prolonged stimulation of the gland were different.3. The time course of amylase secretion in response to an optimal dose of ACh (10(-5)m) was characterized by an initial rapid increase followed by a slow sustained rise. For caerulein (10(-8)m), an initial rapid rise was followed either by a plateau or slight decline in the rate of amylase secretion.4. Both secretagogues produced similar increases in the rate coefficient of (45)Ca efflux from the gland.5. With supra-optimal doses of the secretagogues, amylase secretion, but not the rate coefficient of (45)Ca efflux, was depressed.6. Reducing the extracellular Ca(2+) concentration did not have a marked effect on basal amylase secretion but inhibited the action of both secretagogues. When the Ca(2+) concentration was 10(-6)m or lower, these inhibitory effects were irreversible. Amylase secretion stimulated by ACh was more sensitive to extracellular Ca(2+) deprivation than that stimulated by caerulein, the concentration required for half-maximal secretion being about 9-fold greater for ACh.7. Decreasing the extracellular Ca(2+) concentration increased both the basal and stimulated rate coefficients of (45)Ca efflux.8. Our results support the hypothesis that pancreatic enzyme secretagogues act by releasing bound Ca(2+) from sites within the acinar cell. Furthermore, they suggest that the site utilized by ACh is more amenable to depletion, via changes in extracellular Ca(2+) concentration, than that employed by caerulein.