Secretagogue-induced changes in system A amino acid transport in the rat exocrine pancreas: stimulation of 2-methylaminoisobutyric acid efflux by carbachol.

Secretagogue-induced changes in exocrine pancreatic amino acid transport are poorly understood. In this study uptake of the specific non-metabolized System A amino acid analogue 2-methylaminoisobutyric acid (2-MeAIB) was measured in the isolated perfused rat pancreas during 60 min loading with D-[3H]mannitol (extracellular tracer) and 2-[14C]MeAIB. Tracer 2-MeAIB reached a maximal uptake of 37 +/- 4% (n = 4) after 3 min of loading and gradually decreased to a steady-state uptake of 13 +/- 1%. Infusion of carbachol (3.10(-7) M) during the tracer loading period abolished net tracer 2-MeAIB uptake, and reperfusion in the absence of carbachol restored net uptake to the prestimulus value. Less than 41% of the arterial 2-[14C]MeAIB or D-[3H]mannitol activity appeared in the basal pancreatic secretion. Carbachol evoked a 4.8-fold increase in pancreatic juice flow and appeared to reduce the activity of both tracers in the exocrine secretion. During washout of the pancreas with an isotope-free medium 2-[14C]MeAIB cleared from a rapidly exchanging pool with a time constant (tau 1) of 1.4 +/- 0.3 min (n = 4) and a more slowly exchanging pool with a time constant (tau 2) of 20.7 +/- 1.1 min. Carbachol accelerated efflux of 2-[14C]MeAIB from the epithelium but had no effect on the slow phase of D-[3H]mannitol washout. Our findings suggest that activation of cholinergic receptors modifies Na+-dependent System A amino acid transport in the basolateral membrane of the exocrine pancreatic epithelium.