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The role of Ca2+ in protein secretion from the isolated perfused cat's pancreas, the effect of the dibutyryl analogues of cAMP and cGMP, and the interrelation of Ca2+ and the nucleotides were studied. The following results were obtained: 1. Pancreatic enzyme secretion can be elicited by CaCl2 injections into the pancreatic arteries and is linearily related to the peak Ca2+ concentration in the effluent perfusate. Different background Ca2+ concentrations in the perfusate (3 mM or 0.125 mM) do not disturb this relation, indicating that no adaptation occurs. The effect of Ca2+ injections is of the same magnitude as that evoked by the hormones pancreozymin or acetylcholine. 2. Injections of Ca2+ potentiate the effects of dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP), dibutyryl guanosine 3',5'-cyclic monophosphate (dbcGMP) or theophylline. 3. Infusion of low doses of pancreozymin increases the Ca2+ effect. The findings indicate that extracellular Ca2+ is involved in the mechanism of enzyme secretion and that Ca2+ and cyclic nucleotides have a synergistic action on the target.

Transport of alanine was studied in isolated plasma membrane vesicles from cat pancreas using a rapid filtration technique. The uptake is osmotically sensitive and the kinetics of L-alanine transport are biphasic showing a saturable and a nonsaturable component. The saturable component is seen only when a sodium gradient directed from the medium to the vesicular space is present. Under this condition an overshooting uptake of L-but not of D-alanine occurs. The Na+ gradient stimulated uptake of L-alanine is inhibited by L-serine and L-leucine and stimulated when the membrane vesicles had been preloaded with L-alanine, L-serine or L-leucine. The ionophore monensin inhibits stimulation of uptake caused by a sodium gradient. In the presence of valinomycin or carbonyl cyanide p-trifluoromethoxyphenylhydrazone (CFCCP), the sodium-dependent transport is augmented in vesicles preloaded with K2SO4 or H+ ions (intravesicular pH 5.5), respectively. In the presence of different anions, the Na+-dependent transport is stimulated according to increasing anionic penetration through membrane (lipid solubility). We conclude that a sodium dedpendent electrogenic amino acid transport system is present in pancreatic plasma membranes.

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