THE ROLE OF EXTRACELLULAR CALCIUM IN THE SECRETORY RESPONSE OF THE EXOCRINE PANCREAS TO SECRETIN AND FORSKOLIN

Abstract

The influence of extracellular Ca²⁺ on secretin-induced secretory responses (enzyme output andjuice flow) was examined in the isolated perfused rat pancreas. Secretin in the range of 100pM to 10 nM produced dose-dependent secretory responses. The secretin-induced enzyme output was markedly inhibited when CaCl₂ was removed from the perfusing solution, whereas the juice flow by secretin at higher concentrations (1.0 and 10 nM) was not significantly inhibited. Not only the enzyme output but also the juice flow induced by 1 μM forskolin were inhibited in the Ca²⁺-deficient environment. Continuous stimulation with 100 μM dibutyryl cAMP caused a gradual increase in the pancreatic secretory responses. The enzyme output was abolished but the juice flow was slightly inhibited in the Ca²⁺-deficient environment. Continuous stimulation with 1 nM secretin induced a gradual increase in the amount of intracellular cyclic AMP, which was significantly decreased in the Ca²⁺-deficient environment. The present results show that pancreatic enzyme output induced by secretin depends on the extracellular Ca²⁺-concentration. Two possible mechanisms involved in the Ca²⁺-dependent enzyme output were discussed in relation to the two kinds of intracellular second messengers, Ca²⁺ and cyclic AMP.