Secretagogue regulation of Na+-K+ pump activity in pancreatic acinar cells

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Abstract
The effects of secretagogues on Na+-K+ pump activity in dispersed guinea pig pancreatic acinar cells were investigated, using the rate of [3H]ouabain binding as an index of pump turnover. Dispersed acinar cells incubated in HEPES [4-(2-hydroxyethyl)-1-piperazine-N''-2-ethanesulfonic acid] buffered Ringer bound 7.8 .times. 105 ouabain molecules per cell with an equilibrium dissociation constant of 0.86 .mu.M. The rate of [3H]ouabain binding to dispersed cells was both temperature- and Na+-dependent. Carbachol, cholecystokinin octapeptide (CCK8), secretin and vasoactive intestinal peptide (VIP) each stimulated the initial rate of binding in a dose-dependent fashion. Dose-response curves for carbachol and CCK8 were similar to previously determined curves for their effects on protein secretion. Secretin strongly stimulated [3H]ouabain binding, which contrasts to its weak effectiveness in stimulating protein release from these cells; VIP was a much less effective and potent stimulator of [3H]ouabain binding. The response to maximally effective concentrations of CCK8 was not enhanced by carbachol but was enhanced in an additive manner by secretin or VIP. The increase in [3H]ouabain binding elicited by each of the 4 secretagogues was substantially reduced by lowering the medium Na+ concentration from 130-13 mM, whereas deletion of Cl- from the incubation medium had no effect. These studies show that secretagogues stimulate Na+-K+ pump activity in pancreatic acinar cells in a manner consistent with a central role for the pump in fluid and electrolyte secretion. In addition, the secretin-preferring receptor in guinea pig pancreatic acinar cells may principally modulate electrolyte rather than protein secretion.