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No evidence for temperature-dependent changes in the pharmacological specificity ofβ 1- adrenoceptors

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Summary

In rabbit lung membranes known to contain both β1- and β2-adrenoceptors it was studied whether changes in incubation temperature may affect binding characteristics and/or selectivity of β1- and β2-adrenoceptor drugs. For this purpose inhibition of binding of the highly specific β-adrenoceptor radioligand (±)-125iodocyanopindolol (ICYP) by β1- and β2-selective as well as non-selective drugs was determined at incubation temperatures of 37° C and 18° C and analyzed by Hofstee-plots.

  1. 1.

    The density of β-adrenoceptors in rabbit lung membranes was identical independently of the incubation temperature.

  2. 2.

    Atboth incubation temperatures β1- and β2-selective drugs showed biphasic displacement curves and non-linear Hofstee-plots, while inhibition of binding by the non-selective drugs resulted in monophasic displacement curves with linear Hofstee-plots. With decreasing temperature affinity of antagonists to β-adrenoceptors increased only slightly, while affinity of agonists increased markedly.

  3. 3.

    Forall β1- and β2-selective drugs thesame ratio β1-/β2-adrenoceptors was calculated from the Hofstee-plots independently of the incubation temperature: It amonunted to about 80% β1- and 20 % β2-adrenoceptors in rabbit lung.

  4. 4.

    At an incubation temperatur of 37°C the displacement curve of the agonist isoprenaline was biphasic in the absence of GTP with a non-linear Hofstee-plot indicating that at 37°C isoprenaline binds to high and low affinity states of the β-adrenoceptors in rabbit lung. At 18°C, however, β-adrenoceptors do not form the high affinity GTP-sensitive complex with agonists, since GTP had no influence on isoprenaline displacement curves.

  5. 5.

    It is concluded that a decrease in the incubation temperature of ICYP binding assay from 37°C to 18°C does neither alter the relative amount of β1- and β2-adrenoceptors in rabbit lung membranes nor the selectivity of β1- and β2-selective adrenoceptor drugs.

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Abbreviations

(−)-3H-DHA:

(−)-3H-dihydroalprenolol

(±)-ICYP:

(±)-125iodocyanopindolol

(±)-IHYP:

(±)125iodohydroxybenzylpindolol

GTP:

guanosine-5′-triphosphate

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Authors and Affiliations

  1. Division of Renal and Hypertensive Diseases, Medizinische Klinik und Poliklinik, University of Essen, Hufelandstrasse 55, D-4300, Essen, Germany

    Otto-Erich Brodde, Frank Kuhlhoff, Jacqueline Arroyo & Axel Prywarra

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  1. Otto-Erich Brodde
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  2. Frank Kuhlhoff
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  3. Jacqueline Arroyo
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  4. Axel Prywarra
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Additional information

This work was supported by the SANDOZ-Stiftung für Therapeutische Forschung

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Brodde, OE., Kuhlhoff, F., Arroyo, J. et al. No evidence for temperature-dependent changes in the pharmacological specificity ofβ 1- adrenoceptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 322, 20–28 (1983). https://doi.org/10.1007/BF00649347

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  • DOI: https://doi.org/10.1007/BF00649347

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