Dependence of pancreatic enzyme secretion on extracellular Ca⁺⁺ and its modification by cyclic nucleotides and thyrocalcitonin

Pancreatic enzyme secretion of the same magnitude as that evoked by the hormones pancreozymin or acetylcholine, can be elicited by CaCl2 injections into the pancreatic arteries. Injections of CaCl2 together with dibutyryl adenosine 3'5' cyclic monophosphate (dbcAMP) or dibutyryl guanosine 3'5' cyclic monophosphate (dbcGMP) produces a greater effect on enzyme output than injection of either substance alone. During a background infusion of low doses of acetylcholine plus atropine, injections of the same doses of CaCl2 cause a higher enzyme output than injection of CaCl2 without acetylcholine plus atropine. The effect of CaCl2 injections was also enhanced during theophylline infusion. These findings indicate that cAMP or cGMP, or both are involved in the mechanism of enzyme secretion, and that Ca++ and cyclic nucleotides together have a synergistic action on the target, and are probably the key substances in eliciting enzyme secretion. Thyrocalcitonin inhibits the enzyme secretion induced either by pancreozymin injection, by acetylcholine injection or by rapid elevation of external Ca++. As the effect of CaCl2 injections is more markedly inhibited by thyrocalcitonin than the effect of the hormones, it is suggested that thyrocalcitonin inhibits the passive influx of Ca++ into the cell