Dopamine receptor modulation of noradrenaline release by carmoxirole in human cortical kidney slices

Abstract

The effect of the dopamine D2-receptor agonist carmoxirole on noradrenaline release was investigated in human and rat cortical kidney slices. After preincubation with 3H-noradrenaline, the slices were electrically stimulated at 5 Hz in superfusion chambers, and the stimulation-induced (S-I) outflow of radioactivity was taken as the index of noradrenaline release. In human but not in rat cortical kidney slices, carmoxirole (0.03 microM) inhibited the S-I outflow of radioactivity. Carmoxirole (0.3 microM) also failed to inhibit the S-I outflow of radioactivity from human kidney slices. When alpha-adrenoceptors were blocked by the non-selective alpha-adrenoceptor antagonist phentolamine (1 microM), carmoxirole (0.03 microM, 0.3 microM) inhibited S-I outflow to a similar extent. The inhibitory effect of carmoxirole (0.03 microM) was prevented by the D2-receptor antagonist (-)-sulpiride (10 microM) but not by the D1-receptor antagonist SCH 23390 (1 microM) in human kidney slices. Phentolamine (1 microM) by itself induced a five-fold greater enhancement of the S-I outflow of radioactivity in rat than in human cortical kidney slices. The data suggest that activation of prejunctional D2-receptors by carmoxirole inhibits noradrenaline release from human renal sympathetic nerves. Carmoxirole in higher concentrations (0.3 microM) blocks inhibitory prejunctional alpha-autoreceptors, which seems to mask the inhibitory D2-receptor mediated effect. The different effects of phentolamine and carmoxirole in human and rat kidney may indicate a difference of the prejunctional alpha-autoreceptor mechanism in the two species.