Stimulus‐secretion coupling in pancreatic acinar cells: influences of external sodium and calcium on responses to cholecystokinin‐pancreozymin and ionophore A23187

Abstract

1. The roles of Na and Ca ions in stimulus‐secretion coupling were analysed in the isolated and perfused rat pancreas. 2. Partial replacement of NaCl with LiCl produced a diminution in both amylase output and pancreatic juice flow which were induced by 5 m‐u. CCK‐PZ/ml., and almost normal responses were usually regained immediately after the reintroduction of a standard concentration of NaCl. Nearly total replacement of NaCl with LiCl caused an almost complete inhibition of the responses, although 25 m M‐NaHCO₃ and 1 m M‐NaH₂PO₄ were still present, and only partial recovery was obtained after the re‐introduction of a standard concentration of NaCl. 3. A quantitative relationship was found between the amount of amylase released by CCK‐PZ and the [Na⁺]_o over the range 26‐157 m M in the presence of 2·5 m M‐Ca. A similar relationship was also observed when [Ca²⁺]_o was decreased to 1·0 m M, but the responses were reduced to about one half of those observed with 2·5 m M‐Ca. 4. The most satisfactory theory which explains the cellular mechanism of CCK‐PZ‐induced amylase output, and which fits the experimental data, requires the dominant activity of a complex composed of a carrier molecule bearing one Ca and four Na molecules, if there is no interaction between Na⁺ and Li⁺. 5. A quantitative relationship was also found between the amount of pancreatic juice flow stimulated by CCK‐PZ and [Na⁺]_o, over the range 26‐157 m M, in the presence of 1·0 or 2·5 m M‐Ca. 6. A similar quantitative relationship was found between the amount of amylase released by Ca‐ionophore A23187 and [Na⁺]_o in the presence of 2·5 or 5·0 m M‐Ca. The most satisfactory theory which fits this experimental data also requires the dominant activity of a complex composed of a carrier molecule bearing one Ca and four Na molecules, if there is no interaction between Na⁺ and Li⁺.