Methoxamine inhibits noradrenaline release through activation of alpha 1- and alpha 2-adrenoceptors in rat isolated kidney: involvement of purines and prostaglandins.
The effects of the alpha 1-adrenoceptor agonist methoxamine and the alpha 2-adrenoceptor agonist bromoxidine (UK 14034) on the stimulation induced (S-I) outflow of radioactivity at 100 Hz/6 pulses from rat isolated kidney preincubated with 3H-noradrenaline were investigated. Methoxamine (0.3-30 mumol/l) inhibited S-I outflow of radioactivity to a maximum of 83% with a pEC50 of 5.85 (5.71-5.94). UK 14304 (0.0003-0.3 mumol/l) inhibited S-I outflow of radioactivity to a maximum of 99% with a pEC50 of 8.35 (8.26-8.47). alpha-Adrenoceptor antagonist affinities (pKD) against methoxamine and UK 14304 at prejunctional alpha-adrenoceptors were determined. The concentration response curve of methoxamine was shifted to the right by the alpha 1/alpha 2B-adrenoceptor antagonist prazosin (0.1 mumol/l) with a pKD of 7.41 and that of UK 14304 by prazosin (0.3 mumol/l) with a pKD of 6.24. The alpha 2-adrenoceptor antagonist rauwolscine (0.1 mumol/l) shifted the concentration response curve of UK 14304 potently to the right with a pKD of 8.34. The concentration response curve of methoxamine was shifted also to the right by rauwolscine (0.1 mumol/l) and the alpha 2-adrenoceptor antagonist idazoxan (0.1 mumol/l), however, both antagonists suppressed the maximum response of methoxamine to 46% and 56%, respectively. A ten times lower concentration of rauwolscine (0.01 mumol/l) did not shift the concentration response curve of methoxamine but the inhibitory effect of methoxamine still reached only a maximum of 59%.(ABSTRACT TRUNCATED AT 250 WORDS)
Bohmann
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Medizinische Universitätsklinik Freiburg, Innere Medizin IV, Federal Republic of Germany.
Schollmeyer
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Rump
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LC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D004347:Drug Interactions; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D011453:Prostaglandins / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011453:Prostaglandins; D011687:Purines; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D008729:Methoxamine; D009638:Norepinephrine