Effect of Catecholamines on Amino Acid Transport in Isolated Rat Hepatocytes*

Abstract

The effects of catecholamines on neutral amino acid transport were investigated in freshly prepared suspensions of isolated hepatocytes obtained by enzymatic dispersion of adult rat liver. Steady state, influx, and efflux experiments were carried out with aαamino[l-14C]isobutyric acid (AIB) and [l-14C]cycloleucine. Epinephrine, phenylephrine, and isoproterenol increased the concentrative uptake of AIB; only the influx was affected. A pre-exposure of cells to adrenergic compounds for at least 2 h was required to observe maximal stimulation of transport. The order of potency according to ED50 values for stimulation of AIB transport was epinephrine (0.08 μM) > norepinephrine (0.3 μM) > phenylephrine (1.6 μM) > isoproterenol (10 μM). Epinephrine increased the Vmax of the sodium-dependent component of AIB transport without affecting the Km. Cycloheximide and, to a lesser extent, actinomycin D inhibited the catecholamine stimulation of transport. The a antagonist phentolamine virtually abolished the stimulation of AIB influx by epinephrine and phenylephrine, whereas the β antagonist propranolol had little effect. The effect of isoproterenol was partially inhibited by both antagonists. Under conditions which allow for discrimination between the A and L transport systems, catecholamines were found to stimulate only the A system. It is concluded that: 1) catecholamines directly stimulate amino acid transport in freshly isolated rat hepatocytes; 2) this effect is exerted mainly through a adrenergic mediation; 3) the stimulation is restricted to the A system of transport; and 4) the effect involves new protein synthesis. (Endocrinology102: 379, 1978).