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Release-inhibiting α2-adrenoceptors at serotonergic axons in rat and rabbit brain cortex: evidence for pharmacological identity with α2-autoreceptors

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Abstract

The pharmacological properties of the presynaptic α2-adrenoceptors modulating the release of serotonin in rat and rabbit brain cortex (α2-heteroreceptors) were compared with the properties of presynaptic α2-autoreceptors in the same brain area. Brain cortex slices were preincubated with [3H]-serotonin or [3H]-noradrenaline and then superfused and stimulated by brief high-frequency pulse trains.

The α2-adrenoceptor agonist bromoxidine reduced the electrically evoked overflow of tritium in experiments with both [3H]-noradrenaline and [3H]-serotonin and in brain slices from either species. The antagonists phentolamine, idazoxan, (+)-mianserin, rauwolscine, 5-chloro-4(1-butyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2-amine (ORG 20350), 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101), (−)-mianserin and corynanthine caused parallel shifts of the concentration-inhibition curves of bromoxidine to the right. Negative logarithms of antagonist dissociation constants pKd were calculated from the shifts. In the rat, the α2-autoreceptor pKd value of each single antagonist was similar to its α2-heteroreceptor pKd value, maximal difference 0.4, giving a close correlation, r = 0.97 (P<0.001). In the rabbit equally, the α2-autoreceptor pKd value of each single antagonist was similar to its α2-heteroreceptor pKd value, maximal difference 0.4, again yielding a close correlation, r = 0.96 (P < 0.001). However, antagonist pKd values at rat α2-autoreceptors differed from those at rabbit α2-autoreceptors, r = 0.70 (P > 0.05), and antagonist pKd values at rat α2-heteroreceptors differed from those at rabbit α2-heteroreceptors, r = 0.64 (P > 0.05). Comparison with radioligand binding experiments from the literature indicated that, in the rat, both auto- and heteroreceptors conformed best to the α2D subtype (r ⪖ 0.97, P < 0.01 for pKd correlation with binding sites in rat submaxillary gland) whereas, in the rabbit, they conformed best to the α2A subtype (r ⪖ 0.93, P < 0.01 for pKd correlation with binding sites in HT29 cells).

It is concluded that, in both the rat and the rabbit, the α2-adrenoceptors modulating the release of serotonin are pharmacologically identical with the presynaptic α2-autoreceptors. However, rat α2-autoreceptors and -heteroreceptors differ pharmacologically from rabbit α2-autoreceptors and -heteroreceptors. Presynaptic α2-auto-as well as -heteroreceptors are α2D in the rat and α2A in the rabbit.

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität, Hermann-Herder-Strasse 5, D-79104, Freiburg i. Br., Germany

    Anne-Ulrike Trendelenburg, Marie Trendelenburg, Klaus Starke & Norbert Limberger

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  1. Anne-Ulrike Trendelenburg
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  2. Marie Trendelenburg
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  3. Klaus Starke
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  4. Norbert Limberger
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Correspondence to: N. Limberger at the above address

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Trendelenburg, AU., Trendelenburg, M., Starke, K. et al. Release-inhibiting α2-adrenoceptors at serotonergic axons in rat and rabbit brain cortex: evidence for pharmacological identity with α2-autoreceptors. Naunyn-Schmiedeberg's Arch Pharmacol 349, 25–33 (1994). https://doi.org/10.1007/BF00178202

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