title: Dopamine DA2-receptor activation inhibits noradrenaline release in human kidney slices.
abstract: Dopamine receptor modulation of noradrenaline release from renal sympathetic nerves was investigated. Human kidney slices were incubated with 3H-noradrenaline, placed into superfusion chambers between two platinum electrodes and field-stimulated at 5 Hz. The slices accumulated radioactivity. Pretreatment of the kidney slices with 6-hydroxy-dopamine (1.2 mM) prior to the 3H-noradrenaline incubation reduced the accumulation of radioactivity. The stimulation induced (S-I) outflow of radioactivity was mainly composed of intact 3H-noradrenaline. The sodium channel blocker tetrodotoxin (1 microM), 6-hydroxy-dopamine pretreatment and omission of calcium from the superfusion solution abolished S-I outflow of radioactivity. The DA1-receptor agonist fenoldopam (SKF 82526; 0.01 and 0.1 microM) did not alter but fenoldopam (1 microM) increased S-I outflow of radioactivity. However, in the presence of either the non-selective alpha-adrenoceptor antagonist phentolamine (1 microM) or the selective alpha 2-adrenoceptor antagonist idazoxan (1 microM) fenoldopam (1 microM) had no effect. The DA2-receptor agonist quinpirole (LY 171555; 1 microM) inhibited S-I outflow of radioactivity, an effect blocked by the selective DA2-receptor antagonists S(-)-sulpiride (10 microM) and domperidone (0.3 microM) but unaltered either by the DA1-receptor antagonist SCH 23390 (1 microM) or by phentolamine (1 microM). The alpha 2-adrenoceptor agonist UK 14304 (0.1 microM) inhibited S-I outflow of radioactivity, and this effect was blocked by phentolamine (1 microM) and idazoxan (1 microM) but unaltered by S(-)-sulpiride (10 microM). Phentolamine and idazoxan, in contrast to S(-)-sulpiride, domperidone and SCH 23390, enhanced S-I outflow of radioactivity by themselves.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Medizinische und Chirurgische Universitätsklinik Freiburg, Germany.
authors.forename: L C
authors.initials: LC
authors.lastname: Rump
authors.forename: E
authors.initials: E
authors.lastname: Schwertfeger
authors.forename: M J
authors.initials: MJ
authors.lastname: Schuster
authors.forename: U
authors.initials: U
authors.lastname: Schaible
authors.forename: A
authors.initials: A
authors.lastname: Frankenschmidt
authors.forename: P J
authors.initials: PJ
authors.lastname: Schollmeyer
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D018818:Fenoldopam; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D019257:Quinpirole; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015259:Dopamine Agents; D004873:Ergolines; D007211:Indoles; D011725:Pyridines; D011810:Quinoxalines; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D013779:Tetrodotoxin; D000068438:Brimonidine Tartrate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D016627:Oxidopamine; D018818:Fenoldopam; C071485:carmoxirole; D002118:Calcium; D009638:Norepinephrine