Rat pancreas adenylate cyclase: VII. Effect of extracellular calcium on pancreozymin-induced cyclic AMP formation.

1. The effect of stimulation of adenylate cyclase by pancreozymin-C-octapeptide on the cyclic AMP level of rat pancreatic fragments has been investigated. 2. In normal Krebs-Ringer bicarbonate medium pancreozymin-C-octapeptide causes a slight increase in pancreatic cyclic AMP level; this increase can be considerably enhanced by incubation in a calcium-free incubation medium. 3. The dose-response curve for pancreozymin-C-octapeptide in calcium-free medium is shifted to lower peptide concentrations, compared to the curve in normal Krebs-Ringer bicarbonate medium. 4. The maximal stimulatory effect of pancreozymin-C-octapeptide is obtained at a 1-methyl-3-isobutylxanthine concentration of 10 mM. 5. It suffices to lower the Ca2+-concentration of the medium from 2.5 to 1.5 mM to get the maximal increase in cyclic AMP content under influence of pancreozymin-C-octapeptide. 6. It is concluded that extracellular calcium antagonizes the stimulation of adenylate cyclase by pancreozymin-C-octapeptide. This suggests that a low cytoplasmic Ca2+-concentration is required for the maximal response of acinar cell adenylate cyclase to pancreozymin.