Influences of ionic environments on ACh-induced secretory responses in isolated perfused pancreas of rats.

The influence of extracellular Ca2+ concentration, [Ca2+]o, on the secretory response to acetylcholine (ACh) was analyzed in isolated perfused rat pancreas. The decrease of [Ca2+]o strongly diminished the amylase output and pancreatic juice flow in response to continuous stimulation with 5 X 10(-8) M ACh. A quantitative relation was found between the amount of amylase release by 5 X 10(-8) M ACh and the [Ca2+]o over a range of 0.1--2.5 mM. The partial replacement of NaCl with LiCl produced a diminution in both amylase output and pancreatic juice flow. A quantitative relation existed between the amount of ACh-induced amylase release and the [Na+]o over a range of 86--157 mM. The partial replacement of KCl with NaCl produced falls in both amylase output and pancreatic juice flow. Again, a quantitative relation existed between ACh-induced amylase release and [K+]o over a range of 1.0--5.6 mM. These results are compatible with the view that both the amylase output and the juice flow induced by 5 X 10(-8) M ACh are proportional to the amount of carrier-Ca complex and that the inward movement of the complex may be linked closely to the activation of Na pumps on the pancreatic acinar cell. A dose-response relation was found between the concentration of ACh and the amylase output. The relation was shifted to the left when 1 mU/ml cholecystokinin-pancreozymin (CCK-PZ) was added. A similar shift was observed when 1 mU/ml secretin was added. These results support the view that ACh, CCK-PZ, and secretin may activate the common cellular process in stimulus-secretion coupling, although these secretagogues may severally act on the different receptor sites.