title: Effects of imidazolines on noradrenaline release in rat isolated kidney.
abstract: The aim of the present study was to investigate whether or not activation of imidazoline receptors modulates noradrenaline release in the rat isolated kidney. Kidneys were pre-exposed to 3H-noradrenaline and the renal nerves were stimulated with 6 pulses at 100 Hz. The stimulation induced (S-I) outflow of radioactivity was taken as an index of endogenous noradrenaline release. The imidazoline derivatives clonidine (1-1000 nmol/l) and moxonidine (10-1000 nmol/l) inhibited S-I outflow of radioactivity with an EC50 of 6.8 nmol/l and 62.5 nmol/l and a maximum of 88% and 97%, respectively. The concentration response curves for clonidine and moxonidine were shifted to the right by the selective alpha 2-adrenoceptor antagonist rauwolscine (0.1 mumol/l) in a parallel manner with identical pKB's of 8.52 and 8.46, respectively. Furthermore, the alpha-adrenoceptor agonist (-)-alpha-methylnoradrenaline (0.1-30 nmol/l), which has no affinity for imidazoline binding sites, inhibited S-I outflow of radioactivity with and EC50 of 2.4 nmol/l and a maximum of 94%. Rauwolscine (0.1 mumol/l) again shifted the concentration response curve for this alpha-adrenoceptor agonist to the right with a pKB of 8.40. Moreover, the selective alpha 2-adrenoceptor antagonist 2-[2-(2-methoxy-1,4- benzo-dioxanyl)]imidazoline HCl (RX821002, 0.01 mumol/l) shifted the concentration response curves for clonidine and moxonidine to the right with pKB's of 9.46 and 9.18, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Medizinische Universitätsklinik Freiburg, Innere Medizin IV, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bohmann
authors.forename: P
authors.initials: P
authors.lastname: Schollmeyer
authors.forename: L C
authors.initials: LC
authors.lastname: Rump
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D054833:Isoindoles; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008297:Male; D008771:Nordefrin / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D007093:Imidazoles; D054833:Isoindoles; D015016:Yohimbine; C036966:4-chloro-2-(2-imidazolin-2-ylamino)isoindoline; C043482:moxonidine; D003000:Clonidine; D008771:Nordefrin; D009638:Norepinephrine