Dopamine receptor modulation of noradrenaline release by carmoxirole in human cortical kidney slices.
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.
Rump
L C
LC
Universitätsklinik Freiburg, Germany.
Schwertfeger
E
E
Schaible
U
U
Schuster
M J
MJ
Frankenschmidt
A
A
Schollmeyer
P
P
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D001552:Benzazepines; D015259:Dopamine Agents; D007211:Indoles; D011725:Pyridines; D011954:Receptors, Dopamine; D013469:Sulpiride; C071485:carmoxirole; D009638:Norepinephrine; D010646:Phentolamine