Histamine H3 receptor-mediated inhibition of noradrenaline release in pig retina discs |
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Authors: | Eberhard Schlicker Walter Schunack Manfred Göthert |
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Institution: | (1) Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität, Bonn, Reuterstrasse 2b, W-5300 Bonn 1, Federal Republic of Germany;(2) Institut für Pharmazie, Freie Universitat Berlin, Königin-Luise-Strasse 2 + 4, 1000 Berlin 33 |
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Abstract: | Summary Discs of pig retina were preincubated with 3H-noradrenaline, 3H-dopamine or 3H-serotonin and then superfused. Electrical field stimulation increased the outflow of tritium from discs preincubated with 3H-noradrenaline or 3H-dopamine, but no from discs preincubated with 3H-serotonin. The tritium content at the end of superfusion was similar in discs preincubated with 3H-noradrenaline or 3H-dopamine but about tenfold lower in discs preincubated with 3H-serotonin. The tritium content in discs preincubated with 3H-noradrenaline was markedly reduced when desipramine was present during preincubation but was not affected by selective inhibitors of dopamine and serotonin uptake. The tritium content in discs preincubated with 3Hdopamine and 3H-serotonin, in contrast, was reduced or tended to be reduced by a selective dopamine and serotonin uptake inhibitor, respectively.The electrically evoked overflow of tritium from discs preincubated with 3H-noradrenaline was abolished by tetrodotoxin or omission of Ca2+. In discs superfused with desipramine, the electrically evoked overflow was enhanced by phentolamine but not affected by histamine. When both desipramine and phentolamine were present in the superfusion medium, histamine inhibited the evoked overflow (pIC15 6.85). This effect was mimicked by the histamine H3 receptor agonist R-(–)- -methylhistamine as well as by its S-(+)-enantiomer (pIC15 7.85 and 5.30, respectively) but not by the H1 receptor agonist 2-(2-thiazolyl)ethylamine and the H2 receptor agonist dimaprit (each 10 mol/l). The inhibitory effect of histamine was abolished by the H3 receptor antagonist thioperamide 0.32 mol/l and attenuated by impromidine 3.2 mol/l but not affected by the H1 receptor antagonist dimetindene 3.2 mol/l and the H2 receptor antagonist ranitidine 10 mol/l.The results suggest that, in the pig retina, noradrenaline is taken up into, and released from, noradrenergic neurones (most likely vascular postganglionic sympathetic nerve fibres, less probably tissue-specific noradrenergic neurones of the retina) and that noradrenaline release is subject to modulation via H3 receptors and probably also a-adrenoceptors.Send offprint requests to E. Schlicker at the above address |
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Keywords: | Pig retina Noradrenaline release Histamine H3 receptors R-(– )- -Methylhistamine" target="_blank">gif" alt="agr" align="BASELINE" BORDER="0">-Methylhistamine Thioperamide |
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