Amino acid transport in the rat exocrine pancreas. II. Inhibition by lanthanum and tetracaine.

The two calcium antagonistic agents lanthanum and tetracaine cause severe disturbances in the secretory process of the exocrine pancreas, including inhibition of the rate of protein synthesis and exocytosis. The former effect resulted mainly from the inhibition of amino acid transport. Lanthanum in a concentration up to 1 mM inhibited transport of different species of amino acids in an unspecific way whereas tetracaine interfered specifically with the Na+ -dependent transport system for neutral amino acids (14C-alpha-amino-isobutyric acid). Na+ -dependent transport of neutral amino acids (3H-leucine) was not affected. Transport inhibition was correlated to the acitvity of the Na+, K+ -ATPase system which was measured in isolated plasma membrane fractions. At higher concentrations (5-10 mM) some uptake of lanthanum into the cells by limited endocytosis was observed. At lower concentrations lanthanum seemed to bind exclusively to certain components of the plasms membrane, mainly at the lateral and basal cell surface. Even at a concentration of 5-10 mM no binding to the apical surface occurred. Similarly no binding of lanthanum was observed to the limiting membrane of isolated zymogen granules, while mitochondria, contained in the same fraction showed considerable binding affinity. The action of lanthanum and tetracaine on membrane carrier systems did not affect the interior organization of the plasma membrane. Particle density and distribution in freeze-fracture replicas as well as the submembrane microfilamentous=microtubular system and the junctional elements remained unaffected.