Role of calcium in exocrine pancreatic secretion. II. Comparison of the effects of carbachol and the inophore A-23187 on enzyme secretion and calcium movements in rabbit pancreas.

1. The secretory effects of carbachol and the ionophore A-23187 on the isolated rabbit pancreas and rabbit pancreas fragments are compared in order to obtain more insight in the involvement of calcium in the stimulus-secretion coupling of pancreatic enzyme secretion. 2. The divalent cation ionophore A-23187 mimicks the effect of carbachol on pancreatic enzyme secretion in both preparations. 3. The action of the ionophore is dependent on the presence of extracellular calcium. The carbachol effect is much less dependent on calcium, as it occurs even in a Ca2+ -free medium containing 10(-4) M ethyleneglycol-bis(beta-aminoethylether)-N,N-tetraacetic acid. 4. Carbachol causes a marked increase in the 45Ca2+ efflux from pre-loaded pancreas fragments in both a normal Krebs-Ringer bicarbonate medium and this Ca2+ -free medium. 5. Although the tissue still contains about 50% of its original 45Ca2+ content, at the time of stimulation, the ionophore has little or no effect on the 45Ca2+ efflux. This indicates that the cytoplasmic 45Ca2+ concentration is very low, and hence that most of the 45Ca2+ must be sequestered in one or more intracellular stores. 6. It is concluded that both substances stimulate pancreatic enzyme secretion by increasing the cytoplasmic calcium concentration, through an increase in the calcium permeability of the plasma membrane in the case of the ionophore, and through a release of Ca2+ from intracellular stores in the case of carbachol.