Cellular mechanisms of renal tubular transport of I-dopa and its derivatives in the rat: microperfusion studies.
Proximal tubular transport of L-3,4-dihydroxyphenylalanine (L-dopa) and its derivatives were studied in the rat kidney by microperfusion and capillary perfusion techniques in situ. With the use of microperfusion techniques alone, it was found that L-dopa, L-3-methoxy-4-hydroxyphenylalanine, L-tyrosine and L-phenylalanine rapidly disappeared from the perfusate. The rates of reabsorption were calculated to be 2.05 X 10(-12), 2.13 X 10(-12), 6.35 X 10(-12) and 7.14 X 10(-12) mol/cm/sec, respectively. In contrast, L-alpha-methyldopa and dopamine were only slightly reabsorbed. The permeability coefficients were calculated to be 0.35 X 10(-4) and 0.21 x 10(-4) and 0.21 x 10(-4) cm/sec, respectively. The rate of reabsorption of L-dopa was greatly reduced in the presence of L-phenylalanine in the perfusate, but was not affected by D-dopa. With the stop-flow microperfusion technique with simultaneous capillary perfusion, the zero net flux transtubular concentration difference (deltaC) of labeled dopa was measured. When the initial concentration of 2 mM labeled L-dopa was perfused, the luminal concentration fell to a plateau level of 1.5 mM after a contact time of 20 seconds; i.e., deltaC was 0.5 mM. The net flux was much less than the efflux, suggesting the presence of a secretory or passive back flux of L-dopa. The deltaC of L-dopa was not influenced by the decarboxylase inhibitor, MK-486, and monoamine oxidase inhibitor, pheniprazine, but was significantly reduced by NaCN. Thus the reabsorption of L-dopa in the proximal convoluted tubule is an active process with great structural specificity.
Cellular mechanisms of renal tubular transport of I-dopa and its derivatives in the rat: microperfusion studies. Proximal tubular transport of L-3,4-dihydroxyphenylalanine (L-dopa) and its derivatives were studied in the rat kidney by microperfusion and capillary perfusion techniques in situ. With the use of microperfusion techniques alone, it was found that L-dopa, L-3-methoxy-4-hydroxyphenylalanine, L-tyrosine and L-phenylalanine rapidly disappeared from the perfusate. The rates of reabsorption were calculated to be 2.05 X 10(-12), 2.13 X 10(-12), 6.35 X 10(-12) and 7.14 X 10(-12) mol/cm/sec, respectively. In contrast, L-alpha-methyldopa and dopamine were only slightly reabsorbed. The permeability coefficients were calculated to be 0.35 X 10(-4) and 0.21 x 10(-4) and 0.21 x 10(-4) cm/sec, respectively. The rate of reabsorption of L-dopa was greatly reduced in the presence of L-phenylalanine in the perfusate, but was not affected by D-dopa. With the stop-flow microperfusion technique with simultaneous capillary perfusion, the zero net flux transtubular concentration difference (deltaC) of labeled dopa was measured. When the initial concentration of 2 mM labeled L-dopa was perfused, the luminal concentration fell to a plateau level of 1.5 mM after a contact time of 20 seconds; i.e., deltaC was 0.5 mM. The net flux was much less than the efflux, suggesting the presence of a secretory or passive back flux of L-dopa. The deltaC of L-dopa was not influenced by the decarboxylase inhibitor, MK-486, and monoamine oxidase inhibitor, pheniprazine, but was significantly reduced by NaCN. Thus the reabsorption of L-dopa in the proximal convoluted tubule is an active process with great structural specificity.