Inhibition of pancreatic alpha-aminoisobutyric acid uptake by cholecystokinin and other secretagogues

Abstract

The uptake of the non-metabolizable amino acid, alpha-aminoisobutyric acid (AIB), by isolated mouse pancreatic acini was studied. AIB was concentrated in acinar cell water by an Na+-dependent mechanism. The protein hormone secretagogues caerulein, cholecystokinin, and gastrin and the cholinergic agent carbachol inhibited AIB uptake by greater than 50% of control. The effect of secretagogues on AIB uptake was maximal at hormone concentrations that are slightly higher than those that are maximal for amylase release, but comparable to those concentrations that maximally increase glucose transport by acini. This inhibition of AIB uptake was mediated by both inhibition of AIB influx and stimulation of AIB efflux. In the presence of Ca2+, the Ca2+ ionophore A23187 mimicked the effect of caerulein on AIB uptake. In the absence of Ca2+, control AIB uptake was markedly decreased and both caerulein and A23187 had no further effects. It was concluded, therefore, that secretagogues known to induce enzyme release by an effect on cellular Ca2+ also decrease AIB uptake and that this effect on uptake is most likely mediated by Ca2+.