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[3H]ICS 205-930 labels 5-HT3 recognition sites in membranes of cat and rabbit vagus nerve and superior cervical ganglion

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Summary

The binding characteristics of [3H]ICS 205-930, a 5-hydroxytryptamine 5-HT3 receptor antagonist, were investigated in membranes prepared from cat and rabbit vagus nerve (VN) and superior cervical ganglion (SCG). The autoradiographic localisation of 5-HT3 recognition sites was also assessed using [3H]ICS 205-930 in slices from cat medulla oblongata, nodose ganglion and vagus nerve.

[3H]ICS 205-930 bound to a homogeneous population of high affinity recognition sites in cat VN: Bmax = 201 ± 43 fmol/mg protein, pKD = 9.26 ± 0.17 and SCG: Bmax = 291 ± 40 fmol/mg, pKD = 9.35 ± 0.80 (n = 3). Competition experiments performed in membranes from cat VN and SCG with agonists and antagonists suggested the presence of a homogeneous population of [3H]ICS 205-930 recognition sites. Competition curves were steep and monophasic and were best fitted by a 1 receptor site model. The following rank order of affinity for [3H]ICS 205-930 binding sites was observed with antagonists: SDZ 206-830 = ICS 205-930 > BRL 43694 > SDZ 206–792 > quipazine > MDL 72222 > metoclopramide > mCPP and agonists: 2-methyl-5-HT = 5-HT > phenylbiguanide. A similar profile was observed for a limited series of compounds in rabbit membranes. Drugs acting at 5-HT1, 5-HT2 and dopamine receptors (domperidone, spiperone and metergoline) showed very low affinities for [3H]ICS 205-930 recognition sites. The sites labelled with [3H]ICS 205-930 in vagus nerve and superior cervical ganglion of both species displayed the pharmacological profile of a 5-HT3 receptor. There was a significant correlation between the rank order of affinity of the tested compounds for [3H]ICS 205-930 recognition sites in cat and rabbit membranes and their rank order of affinity for 5-HT3 receptors from neuroblastoma-glioma NG 108-15 cells. Autoradiographic studies suggest that [3H]ICS 205-930 binding sites are present over and around the nodose ganglion cell somata, along certain fibers of the vagus nerve and in the terminal areas of this nerve in the medullar nucleus of the vagus.

The present data demonstrate that [3H]ICS 205-930 identifies 5-HT3 receptors in preparations of cat and rabbit vagus nerve and superior cervical ganglion.

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Authors and Affiliations

  1. Preclinical Research, Buiding 386/525, Sandoz Ltd, CH-4002, Basel, witzerland

    Daniel Hoyer, Christian Waeber, Angela Karpf, Hans Neijt & Jose M. Palacios

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  1. Daniel Hoyer
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  2. Christian Waeber
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  3. Angela Karpf
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  4. Hans Neijt
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  5. Jose M. Palacios
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Send offprint requests to D. Hoyer at the above address

The present results have been presented in part at the Winter Meeting of the British Pharmacological Society, London, December 20–22, 1988 (Hoyer et al. 1989)

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Hoyer, D., Waeber, C., Karpf, A. et al. [3H]ICS 205-930 labels 5-HT3 recognition sites in membranes of cat and rabbit vagus nerve and superior cervical ganglion. Naunyn-Schmiedeberg's Arch Pharmacol 340, 396–402 (1989). https://doi.org/10.1007/BF00167040

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