Receptor Occupancy and Tissue Response

Abstract

ONE of the cornerstones of all quantitative applications of classical receptor theory has been the postulate that the response of a given organ or tissue is proportional to the number of receptors occupied by the activating agent, and that the maximal response occurs when all receptors are occupied. Although never proved experimentally, and perhaps a priori somewhat unlikely in view of the complex nature of tissue responses, this relationship is necessary if agonist dose – response curves are to be explained in terms of mass-action equilibria, and it provides the basis for differentiating reversible competitive from non-competitive or irreversible inhibition. Basic formulations applying mass-action considerations to the differentiation of types of inhibition are those of Gaddum1, applied largely to tissue and organ responses, and of Linweaver and Burke2, which have been applied both to relatively simple enzyme systems and to complex responses of tissues and of intact animals.

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References

  1. 1

    Gaddum, J. H., J. Physiol., 89, 7P (1937).

  2. 2

    Linweaver, H., and Burke, D., J. Amer. Chem. Soc., 56, 658 (1934).

  3. 3

    Chen, G., and Russell, D., Arch. Int. Pharmacodyn., 84, 176 (1950). Chen, G., and Russell, D., J. Pharmacol. and Exp. Therap., 99, 401 (1950). Graham, J. D. P., and Lewis, G. P., Brit. J. Pharmacol., 8, 54 (1953).

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    Nickerson, M., Pharmacol. Rev., 1, 27 (1949).

  5. 5

    Similar shifts of adrenaline and histamine dose–response curves have been reported to occur after exposure of tissues to dibenamine and SY-28 (N-1-naphthylmethyl-N-ethyl-β-bromoethylamine); see Furchgott, R. F., Pharmacol. Rev., 7, 183 (1955).

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