ABSTRACT
The quantitative relation of calcium and protein secretion was studied on the isolated perfused canine pancreas at different secretory states of hydrokinetic and ecbolic stimulation and various extracellular Ca++-concentrations. 1. Calcium and protein secretion are correlated at both ecbolic and hydrokinetic stimulation as well as by biological or synthetic secretion. 2. Enzyme-associated calcium was estimated at 35 nmol/mg protein and did not vary under differing stimulatory and secretory conditions. 3. During variable concentrations of synthetic secretin basal protein and calcium concentrations in the pancreatic juice show a hyperbolic relationship to the respective rates of fluid secretion. At flow rates beyond 3 ml/5 min the calcium concentrations asymptotically tend to 0.46 mEq/l while protein concentrations nearly decrease to zero. Moreover, the y-intercept of the regressionline correlating the calcium and protein concentrations gives with 0.48 mEq/l Ca++ additional evidence of the existence and magnitude of an enzyme-independent calcium fraction, which seems to remain constant over the whole range of secretory rates. 4. The omission of perfusate calcium does not abolish the calcium-protein correlation either at hydrokinetic or at ecbolic stimulation, but diminishes the enzyme-independent calcium fraction. 5. Enhancing perfusate Ca++-concentrations augments calcium output byt fails in stimulating enzyme secretion. It is concluded that at exclusively hydrokinetic stimulation basal secreted protein with a definite amount of chelated calcium is diluted by variable rates of pancreatic juice containing enzyme independent Ca++ at a constant concentration. During different secretory states of hydrokinetic or ecbolic stimulation the respective proportions of enzyme associated and independent calcium vary, and thus determine changes in the calcium-protein ratios. Extracellular calcium can only influence the non-protein-bound calcium fraction of the pancreatic juice presumably by diffusion from the extracellular fluid through the ductal epithelium rather than by an active secretory mechanism.
Subject(s)
Calcium/metabolism , Pancreas/metabolism , Animals , Calcium-Binding Proteins/metabolism , Dogs , In Vitro Techniques , Kinetics , Pancreas/drug effects , Pancreatic Juice/drug effects , Pancreatic Juice/metabolism , Perfusion/instrumentation , Secretin/pharmacology , Secretory Rate/drug effectsABSTRACT
1. The kinetics of Ca++ and enzyme secretion are of corresponding pattern as well at hydrokinetic as at ecbolic stimulation. 2. Physiological respectively pathophysiologically relevant changes of perfusate Ca++ concentrations do not influence pancreatic Ca++ secretion. Extracellular Ca++ concentrations beyond 12 mEq/1 initiate an enzyme independent Ca++ secretion. 3. Hydrokinetic or ecbolic stimulated pancreatic secretion do not distinguish in calcium/protein ratio. 4. Basal and stimulated enzyme secretion of isolated perfused canine pancreas remain unaffected by increments of extracellular Ca++ concentrations even at pharmacological values. 5. The stimulated enzyme- and Ca++ secretion remain constant during hypocalcemic perfusate conditions but decrease to basal values in Ca++ free media, rapidly and completely reversible by recalcification of the perfusate. 6. The secretin stimulated volume secretion remains unchanged either by extremely hypercalcemic or Ca++ depleted perfusate conditions.