Letter | Published:

Synthetic α-adrenergic agonists are potent α-adrenergic blockers in human platelets

Nature volume 274, pages 819820 (24 August 1978) | Download Citation



ADRENALINE- and noradrenaline-induced aggregation of human platelets1–3 is blocked by the α-adrenergic blocking agents, dihydroergotamine, phentolamine, phenoxybenzamine and dibenamine4–6, suggesting the involvement of α-adrenergic receptors. We have demonstrated that adrenaline and noradrenaline inhibit adenylate cyclase (EC in lysates7 and particles8 of human platelets, an effect also blocked by such α-adrenergic antagonists. Synthetic phenylethylamine and imidazoline derivatives that act as α-adrenergic agonists in various other tissues neither induced primary platelet aggregation nor inhibited adenylate cyclase when added at concentrations up to 100 µM9. α-Adrenergic receptors have been identified in human platelets by binding studies using tritiated dihydroergocryptine10,11 or dihydroergonine12,13. The sites to which the dihydrogenated ergot alkaloids were bound showed the typical pattern of an α-adrenergic receptor with respect to displacement by adrenergic agonists and antagonists. However, there have been some discrepancies between the binding affinities of some α-adrenergic agonists and their biological efficacies concerning platelet aggregation and inhibition of adenylate cyclase. The α-adrenergic agonist, clonidine, displaced dihydroergocryptine from the binding sites with similar10 or even a 10-fold higher affinity11 relative to adrenaline, but clonidine (up to 100 µM) was ineffective in inducing primary platelet aggregation and inhibition of adenylate cyclase9. Similar dissociation constants were obtained for phenylephrine and noradrenaline in binding studies12, but in contrast to the natural compound, phenylephrine (up to 100 µM) was unable to induce a biological response9. We observed similar discrepancies with methoxamine, xylometazoline and oxymetazoline12,13. Agents that undergo the primary reaction of high affinity-binding to the receptor but are unable to induce secondary reactions in the form of biological responses should act as antagonists. We have tested this hypothesis and show here that various agents that are potent α-adrenergic agonists in various other systems are α-adrenergic antagonists in human platelets with respect to adrenaline-induced aggregation and inhibition of adenylate cyclase.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    & J. Physiol., Lond. 169, 82P (1963).

  2. 2.

    Nature 200, 763–764 (1963).

  3. 3.

    & Br. J. Haemat. 10, 78–93 (1964).

  4. 4.

    J. clin. Path. 17, 275–281 (1964).

  5. 5.

    & J. Physiol., Lond. 193, 443–453 (1967).

  6. 6.

    & Acta physiol. scand. 75, 129–138 (1969).

  7. 7.

    , & J. Cyclic Nucleotide Res. 2, 381–392 (1976).

  8. 8.

    , & FEBS Lett. 85, 167–170 (1978).

  9. 9.

    , & Naunyn-Schmiedebergs Arch. Pharmak. 302, 285–291 (1978).

  10. 10.

    , & Life Sci. 21, 1429–1438 (1977).

  11. 11.

    , , & J. Clin. Invest. 61, 395–402 (1978).

  12. 12.

    & Naunyn-Schmiedebergs Arch. Pharmak. 302 (Suppl. R51 (1978).

  13. 13.

    & Klin. Wschr. (in the press).

  14. 14.

    & Life Sci. 20, 595–606 (1977).

  15. 15.

    Nature 194, 927–929 (1962).

Download references

Author information


  1. Pharmakologisches Institut, Universität Heidelberg, Heidelberg, FRG



  1. Search for KARL H. JAKOBS in:

About this article

Publication history






Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.