Summary
The effect of the dopamine D2-receptor agonist carmoxirole on noradrenaline release was investigated in human and rat cortical kidney slices. After preincubation with3H-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 slice, carmoxi-role (0.03 μM) inhibited the S-I outflow of radioactivity. Carmoxirole (0.3 μM) also failed to inhibit the S-I outflow of radioactivity from human kidney slices. When α-adrenoceptors were blocked by the non-selective α-adrenoceptor antagonist phentolamine (1 μM), carmoxirole (0.03 μM, 0.3 μM) inhibited S-I outflow to a similar extent. The inhibitory effect of carmoxirole (0.03 μM) was prevented by the D2-receptor antagonist (−)-sulpiride (10 μM) but not by the D1-receptor antagonist SCH 23390 (1μM) in human kidney slices. Phentolamine (1 μM) 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-re-ceptors by carmoxirole inhibits noradrenaline release from human renal sympathetic nerves. Carmoxirole in higher concentrations (0.3 μM) blocks inhibitory prejunctional α-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 α-autoreceptor mechanism in the two species.
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Rump, L.C., Schwertfeger, E., Schaible, U. et al. Dopamine receptor modulation of noradrenaline release by carmoxirole in human cortical kidney slices. Eur J Clin Pharmacol 44 (Suppl 1), S47–S49 (1993). https://doi.org/10.1007/BF01428393
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DOI: https://doi.org/10.1007/BF01428393