1. The orgin of the calcium secreted by the pancreas has been investigated in vivo in the guinea‐pig by a study carried out in parallel (a) in the juice secreted in response to the injection of either secretin or caerulein and (b) in the pancreatic tissue and in cell fractions isolated thereform. 2. In agreement with previous findings we observed that the concentration of calcium is low in the secretin‐stimulated and high in the caerulein‐stimulated juice. In the latter calcium and protein are proportional (cal0 n‐mole:mg). 3. After I.V. injection of 45Ca the radioactivity decreases rapidly and quasi‐exponentially in the blood plasma. A roughly parallel time course is found in the secretin‐stimulated juice: the evolution of the juice: plasma radioactivity ratio resembles that observed with the extraceullar space marker [3H]D‐sorbitol. In contrast, the time course of 45Ca in plasma and caerulein‐stimulated juice are not proportional: the high levels characteristic of this juice are reached several minutes after the injection and maintained thereafter. This increase is followed ca. 50 min later by the appearance of the newly synthesized [3H]L‐leucine‐labelled proteins. 4. The pancreatic tissue is rich in calcium which is localized primarily in zymogen granules (Ca.36 n‐mole:mg protein) and mitochondria; the soluble cytoplasm is low in calcium. 5. The injected 45Ca accumulates in zymogen granules faster than [3H]L‐leucine‐labelled proteins. The 45Ca:protein ratio of these organelles is considerably lower than that of the caerulein‐stimulated juice. 6. It is concluded (a) that calcium is secreted in to the pancreatic juice in two fractions, one (possibly released by simple diffusion) associated with the electrolyte component, the other with protein of the juice, (b) that zymogen granules are the major, but not the only source of the latter fraction, and (c) that the zymogen granule‐associated calcium joins the exportable proteins some time after their synthesis, possibly in the Golgi complex and/or in the condensing vacuoles.
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