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Pharmacological comparison of the sigma recognition site labelled by [3H]haloperidol in human and rat cerebellum

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Summary

The radioligand binding characteristics of [3H]haloperidol (in the presence of spiperone, 25 nmolL−1) were investigated in rat and human cerebellar membranes.

In both rat and human cerebellar membrane preparations saturation studies with [3H]haloperidol (non-specific binding defined by pentazocine, 10 μmolL−1) demonstrated high affinity saturable specific binding to a homogenous population of binding sites (rat, Bmax 6693 ± 1242 fmol mg−1 protein, pKD 8.33 ± 0.08; human, Bmax 2550 ± 437 fmol mg−1 protein, pKD 8.59 ± 0.11; mean ± SEM, n = 3–6). Competition studies employing a wide range of structurally diverse competing compounds displayed that the [3H]haloperidol binding site was pharmacologically similar in both preparations and comparable to sigma recognition sites previously identified in various tissues originating from different species. In addition, with reference to the potential subtypes of sigma recognition sites, the labelling of these sites by low nanomolar concentrations of [3H]haloperidol provides evidence that they belong to the sigma-1 recognition site subtype.

The present findings suggest that the pharmacology of the rat and human cerebellar sigma recognition site are directly comparable and provides further supporting evidence towards the use of [3H]haloperidol radioligand binding studies in the rat to detect sigma receptor ligands with potential therapeutic activity.

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Authors and Affiliations

  1. Department of Pharmacology, The Medical School, University of Birmingham, B15 2TT, Edgbaston, Birmingham, UK

    J. M. Barnes & N. M. Barnes

  2. Department of Pathology, The Medical School, University of Birmingham, B15 2TT, Edgbaston, Birmingham, UK

    P. C. Barber

  3. Postgraduate Studies in Pharmacology, The School of Pharmacy, University of Bradford, BD7 1DP, Bradford, West Yorkshire, UK

    S. Champaneria, B. Costall, C. D. Hornsby & R. J. Naylor

  4. The Neuropathology Laboratory, Department of Pathology, Western General Hospital, Crewe Road, EH4 2XU, Edinburgh, UK

    J. W. Ironside

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  1. J. M. Barnes
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Barnes, J.M., Barnes, N.M., Barber, P.C. et al. Pharmacological comparison of the sigma recognition site labelled by [3H]haloperidol in human and rat cerebellum. Naunyn-Schmiedeberg's Arch Pharmacol 345, 197–202 (1992). https://doi.org/10.1007/BF00165736

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  • DOI: https://doi.org/10.1007/BF00165736

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