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Methoxamine inhibits noradrenaline release through activation of α1- and α2-adrenoceptors in rat isolated kidney: involvement of purines and prostaglandins

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Summary

The effects of the at-adrenoceptor agonist methoxamine and the α2-adrenoceptor agonist bromoxidine (UK 14034) on the stimulation induced (S-1) outflow of radioactivity at 100 Hz/6 pulses from rat isolated kidney preincubated with 3H-noradrenaline were investigated. Methoxamine (0.3 – 30 μmol/l) inhibited S-1 outflow of radioactivity to a maximum of 83% with a pEC50 of 5.85 (5.71–5.94). UK 14304 (0.0003-0.3 μmol/l) inhibited S-I outflow of radioactivity to a maximum of 99% with a pEC50 of 8.35 (8.26–8.47). a Adrenoceptor antagonist affinities (pKD) against methoxamine and UK 14304 at prejunctional α-adrenoceptors were determined. The concentration response curve of methoxamine was shifted to the right by the α1/α2B-adrenoceptor antagonist prazosin (0.1 μmol/l) with a pKD of 7.41 and that of UK 14304 by prazosin (0.3 μmol/l) with a pKD of 6.24. The α2-adrenoceptor antagonist rauwolscine (0.1 μmol/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 μmol/l) and the α2-adrenoceptor antagonist idazoxan (0.1 μmol/l), however, both antagonists suppressed the maximum response of methoxamine to 466% and 56%, respectively. A ten times lower concentration of rauwolscine (0.01 μmol/l) did not shift the concentration response curve of methoxamine but the inhibitory effect of methoxamine still reached only a maximum of 59%. The concentration response curve of methoxamine obtained in the presence of rauwolscine (0.01 μmol/l) was shifted to the right by further addition of prazosin (0.1 μmol/l) with a pKD of 8.80 but was also shifted to the right by either the purinoceptor antagonist 8-(p-sulfophenyl) theophylline (8-SPT; 100 μmol/l) or the prostaglandin synthesis inhibitor indomethacin (20 μmol/l). These results suggest that methoxamine inhibits S-1 outflow of radioactivity in rat isolated kidney probably through three different mechanisms. 1. Activation of postjunctional α1-adrenoceptors and prostaglandin mediated transjunctional inhibition. 2. Activation of postjunctional α2-adrenoceptors and purine mediated transjunctional inhibition. 3. Activation of prejunctional inhibitory α2-adrenoceptors at which methoxamine seems to be a partial agonist.

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Authors and Affiliations

  1. Innere Medizin IV, Medizinische Universitätsklinik Freiburg, Hugstetter Strasse 55, W-7800, Freiburg, Federal Republic of Germany

    C. Bohmann, P. Schollmeyer & L. C. Rump

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  1. C. Bohmann
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  2. P. Schollmeyer
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  3. L. C. Rump
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Correspondence to L. C. Rump at the above address

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Bohmann, C., Schollmeyer, P. & Rump, L.C. Methoxamine inhibits noradrenaline release through activation of α1- and α2-adrenoceptors in rat isolated kidney: involvement of purines and prostaglandins. Naunyn-Schmiedeberg's Arch Pharmacol 347, 273–279 (1993). https://doi.org/10.1007/BF00167445

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