Letter | Published:

Agonist regulation of the human platelet α-adrenergic receptor

Nature volume 274, pages 703706 (17 August 1978) | Download Citation

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Abstract

PROLONGED exposure to drugs or hormones may result in diminished physiological responsiveness which is referred to as tolerance or desensitisation. One mechanism which has been proposed to explain tolerance is a change in the state of tissue receptors following activation by drugs or hormones1. The receptor desensitisation hypothesis to explain tolerance to the β-adrenergic effects of catecholamines has been particularly well characterised in the frog erythrocyte1–4. In contrast, the regulation of catecholamine α-adrenergic receptor-mediated responses has been much less extensively investigated. Although the development of rapid desensitisation or tachyphylaxis is not a prominent feature of many α-adrenergic responses, rat parotid cells lose their α-adrenergic mediated potassium secretory response after 2–4 min of (−)adrenaline exposure5. Concomitantly, there was a decrease in binding of the α-adrenergic antagonist 3H-dihydroergocryptine to these cells which was thought to represent either a decrease in number or affinity of α-adrenergic receptors. It has been hypothesised that α- as well as β-adrenergic responses in man diminish with chronic exposure to high concentrations of catecholamines6. The human platelet would seem to be a useful tissue to investigate this possibility, as catecholamine-induced platelet aggregation is mediated through α-adrenergic receptors. We have recently characterised the human platelet α-adrenergic receptor by ligand binding assay using 3H-dihydroergocryptine and have shown good correlation between binding characteristics and the biochemical and physiological manifestations of α-adrenergic receptor activation7. We now report that the human platelet α-adrenergic receptor is subject to ligand regulation as assessed by 3H-dihydroergocryptine binding and that this regulation is reflected in altered physiological function.

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References

  1. 1.

    , , & Molec. Pharmac. 12, 409–419 (1976).

  2. 2.

    et al. Rec. prog. Horm. Res. 32, 597–630 (1976).

  3. 3.

    , & Proc. natn. Acad. Sci. U.S.A. 72, 1945–1949 (1975).

  4. 4.

    & Proc. natn. Acad. Sci. U.S.A. 73, 1494–1498 (1976).

  5. 5.

    , & J. biol. Chem. 252, 5478–5482 (1977).

  6. 6.

    in Hypertension, (eds Genest, J., Loiw, E. & Kuchel, O.) 781–789 (McGraw-Hill, New York, 1977).

  7. 7.

    , & J. clin. Invest. 61, 1136–1144 (1978).

  8. 8.

    & J. Physiol., Lond. 168, 178–195 (1963).

  9. 9.

    & Thromb. Diath. Haemorrh. 15, 413–419 (1966).

  10. 10.

    & Blood 47, 941–948 (1976).

  11. 11.

    J. Cell Biol. 72, 261–286 (1976).

  12. 12.

    Nature 259, 265–266 (1976).

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Affiliations

  1. Cardiovascular and Hematology Divisions, Peter Bent Brigham Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

    • BARRY COOPER
    • , ROBERT I. HANDIN
    • , LAWRENCE H. YOUNG
    •  & R. WAYNE ALEXANDER

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https://doi.org/10.1038/274703a0

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