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Failure of tyramine to release neuronal ATP as a cotransmitter of noradrenaline in the guinea-pig vas deferens

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Abstract

Contractions, release of noradrenaline and r elease of ATP elicited by the indirectly acting sympathomimetic amine tyramine and responses elicited by exogenous noradrenaline were studied in the isolated vas deferens of the guinea pig. Release of noradrenaline was assessed as overflow of tritium after preincubation with [3H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique.

In tissues pretreated with pargyline 1 mM, tyramine 300 μM, when added to the superfusion medium for 2 min, elicited contraction and an overflow of tritium (mainly [3H]-noradrenaline) and ATP. Contraction and ATP overflow responses were prevented and tritium overflow was greatly reduced by desipramine 10 μM Prazosin 0.3 μM abolished contractions and evoked ATP overflow without changing tritium overflow. Blockade of postjunctional P2-purinoceptors by suramin 300 μM caused a marked decrease of tyramine-evoked contractions and a slight reduction of tritium overflow whereas evoked ATP overflow was markedly increased. The effect on contraction was not shared by two other P2-purinoceptor antagonists, namely pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) 32 μM and diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) 32 μM: PPADS increased contractions about fourfold, whilst DIDS had no effect at all. When the vas deferens was superfused for 24 min with medium containing tyramine 300 μM, evoked contractions and tritium overflow continued throughout whereas ATP overflow faded rapidly to basal values. In the presence of prazosin 0.3 μM, tyramine 300 μM again failed to elicit contractions as well as an overflow of ATP. Application of noradrenaline 10 μM instead of tyramine also resulted in prolonged contraction and an overflow of ATP that declined rapidly.

It is concluded that all ATP released by tyramine is non-neuronal in origin, secondary to the activation of postjunctional α1-adrenoceptors by released noradrenaline. The non-neural ATP does not seem to play a functional role in smooth muscle contraction and derives from a postjunctional source which is subject to a rapid depletion upon sustained α1-adrenoceptor activation.

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Author notes

  1. Jorge GonSalves

    Present address: Lab. Farmacologia, Fac. Farmácia, Universidade do Porto, Rua Anibal Cunha, P-4000, Porto, Portugal

Authors and Affiliations

  1. Pharmakologisches Institut, Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Strasse 5, D-79104, Freiburg, Germany

    Bernd Driessen, Jorge GonSalves & Bela Szabo

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  2. Jorge GonSalves
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  3. Bela Szabo
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Driessen, B., GonSalves, J. & Szabo, B. Failure of tyramine to release neuronal ATP as a cotransmitter of noradrenaline in the guinea-pig vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 353, 175–183 (1996). https://doi.org/10.1007/BF00168755

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