caa a22 4500 469079185 CHVBK 20180323132944.0 cr unu---uuuuu 170328e19920301xx s 000 0 eng 10.1007/BF00168691 doi (NATIONALLICENCE)springer-10.1007/BF00168691 Effects of the novel dopamine DA2-receptor agonist carmoxirole (EMD 45609) on noradrenergic and purinergic neurotransmission in rat isolated kidney [Elektronische Daten] [L. Rump, K. Wilde, C. Bohmann, P. Schollmeyer] Summary: The effects of the classical dopamine DA2-receptor agonist quinpirole (LY 171555) and the recently characterized DA2-receptor agonist, carmoxirole (EMD 45609), on neurotransmission in rat isolated kidney were investigated. After preincubation with 3H-noradrenaline, the renal nerves were electrically stimulated. The stimulation induced (S-I) outflow of radioactivity was taken as an index of noradrenaline release. Quinpirole (0.3 μmol/l) inhibited S-I outflow of radioactivity and pressor responses to renal nerve stimulation (RNS) at 1 Hz. Both effects of quinpirole were blocked by the DA2-receptor antagonist S(−)-sulpiride (10 μmol/l). The α1, α2-adrenoceptor antagonist phentolamine (1 μmol/l) did not block the inhibitory effect of quinpirole. Carmoxirole (0.003 and 0.03 μmol/l) did not alter and carmoxirole (0.3 μmol/l) even enhanced S-I outflow of radioactivity, however, pressor responses to RNS were markedly reduced by carmoxirole (0.003-0.3 μmol/l). Pressor responses to RNS were also markedly reduced by the α1-adrenoceptor antagonist prazosin (0.1 μmol/l). Carmoxirole (0.3 μmol/l), prazosin (0.1 μmol/l) and phentolamine (1 μmol/l) totally abolished pressor responses to exogenous noradrenaline (0.05 μmol/l). In contrast, quinpirole (0.3 μmol/l) did not alter pressor responses to exogenous noradrenaline (0.05 μmol/l). Furthermore, carmoxirole (0.003-0.3 μmol/l) markedly reduced pressor responses induced by the α1-adrenoceptor agonist methoxamine (1 μmol/l) but even the highest concentration of carmoxirole (0.3 μmol/l) had no effect on pressor responses induced by bolus injections of either neuropeptide Y (1.5 ng) or angiotensin II (1 ng). Phentolamine (1 μmol/l) by itself markedly enhanced S-1 outflow of radioactivity and pressor responses to RNS were virtually unchanged. In the presence of phentolamine carmoxirole (0.03 and 0.3 μmol/l) and quinpirole inhibited S-I outflow of radioactivity and pressor responses to RNS. Phentolamine resistant pressor responses to RNS were also inhibited by the P2X-receptor desensitizing agent α, β-methylene adenosine triphosphate (mATP, 1 μmol/l), which by itself in the presence of phentolamine did not alter S-I outflow of radioactivity. The inhibitory effects of carmoxirole (0.3 μmol/l) in the presence of phentolame (1μmol/l) were antagonized by S(−)-sulpiride (10 μmol/l). The data suggest that activation of prejunctional DA2-receptors by quinpirole inhibits noradrenaline release and thereby reduces pressor response to RNS at 1 Hz in rat isolated kidney. Carmoxirole activates prejunctional inhibitory DA2-receptors, but this effect is masked by simultaneous blockade of inhibitory prejunctional α-adrenoceptors. Pressor responses to RNS at 1 Hz in rat isolated kidney are largely due to neuronally released noradrenaline whereas phentolamine resistant pressor responses to RNS at 1 Hz are most likely due to ATP, which is co-released with noradrenaline. Carmoxirole inhibits pressor responses to RNS at 1 Hz as well as pressor responses induced by either exogenous noradrenaline or methoxamine by blocking postjunctional α1-adrenoceptors. In addition carmoxirole and quinpirole seem to block phentolamine resistant pressor responses by inhibiting ATP release through activation of prejunctional DA2-receptors. Springer-Verlag, 1992 Rat kidney nationallicence Prejunctional receptors nationallicence Noradrenaline release nationallicence Dopamine receptors nationallicence α-adrenoceptors nationallicence α ,β-methylene ATP nationallicence Purinergic transmitter nationallicence Rump L. Innere Medizin IV, Medizinische Universitätsklinik Freiburg, Hugstetter Strasse 55, W-7800, Freiburg, Federal Republic of Germany aut Wilde K. Innere Medizin IV, Medizinische Universitätsklinik Freiburg, Hugstetter Strasse 55, W-7800, Freiburg, Federal Republic of Germany aut Bohmann C. Innere Medizin IV, Medizinische Universitätsklinik Freiburg, Hugstetter Strasse 55, W-7800, Freiburg, Federal Republic of Germany aut Schollmeyer P. Innere Medizin IV, Medizinische Universitätsklinik Freiburg, Hugstetter Strasse 55, W-7800, Freiburg, Federal Republic of Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 300-308 0028-1298 345:3<300 1992 345 210 https://doi.org/10.1007/BF00168691 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00168691 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rump L. Innere Medizin IV, Medizinische Universitätsklinik Freiburg, Hugstetter Strasse 55, W-7800, Freiburg, Federal Republic of Germany aut NATIONALLICENCE 700 1- Wilde K. Innere Medizin IV, Medizinische Universitätsklinik Freiburg, Hugstetter Strasse 55, W-7800, Freiburg, Federal Republic of Germany aut NATIONALLICENCE 700 1- Bohmann C. Innere Medizin IV, Medizinische Universitätsklinik Freiburg, Hugstetter Strasse 55, W-7800, Freiburg, Federal Republic of Germany aut NATIONALLICENCE 700 1- Schollmeyer P. Innere Medizin IV, Medizinische Universitätsklinik Freiburg, Hugstetter Strasse 55, W-7800, Freiburg, Federal Republic of Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 300-308 0028-1298 345:3<300 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer