[...]... LLC 3 4 Textbook of Receptor Pharmacology, Second Edition 1.5 Inhibitory Actions at Receptors: I Surmountable Antagonism 41 1.5.1 Overview of Drug Antagonism 41 1.5.1.1 Mechanisms Not Involving the Agonist Receptor Macromolecule 41 1.5.1.2 Mechanisms Involving the Agonist Receptor Macromolecule 42 1.5.2 Reversible Competitive Antagonism 43 1.5.3 Practical Applications of the... 12 Textbook of Receptor Pharmacology, Second Edition [A] and response is here being described rather than explained in terms of a model of receptor action This is an important difference 1.2.3 THE DISTINCTION BETWEEN AGONIST BINDING AND RECEPTOR ACTIVATION Finally, we return to models of receptor action and to a further limitation of the early attempts to account for the shapes of concentration–response... tubocurarine has occupied on average more than 80% of the binding sites on the nicotinic acetylcholine receptors located on the superficial 18 Textbook of Receptor Pharmacology, Second Edition muscle fibers So, when the twitch of the whole muscle has fallen to half its initial amplitude, receptor occupancy by tubocurarine in the surface fibers is much greater than 50% The second complication is that the rate at... [A] { 1 − e − ( k−1 + k+1[ A ])t } K A + [A] (1.21) 20 Textbook of Receptor Pharmacology, Second Edition FIGURE 1.3 The predicted time course of the rise in receptor occupancy following the application of a ligand at the three concentrations shown The curves have been drawn according to Eq (1.22), using a value of 2 × 106 M–1sec–1 for k+1 and of 1 sec–1 for k–1 When t is very great, the ligand and... oversimplification 10 Textbook of Receptor Pharmacology, Second Edition Taking logs, y ⎞ log⎛ ⎟ = log[A] − log K A ⎜ ⎝ 100 − y ⎠ The applicability of this expression (and by implication Eq (1.4)) can be tested by measuring a series of responses (y) to different concentrations of A and then plotting log (y/(100 – y)) against log [A] (the Hill plot) If Equation (1.4) holds, a straight line with a slope of 1 should... .111 Jan Egebjerg Chapter 4 Molecular Structure of Receptor Tyrosine Kinases 131 Steen Gammeltoft Section III: Ligand-Binding Studies of Receptor Chapter 5 Direct Measurement of Drug Binding to Receptors .153 Dennis G. Haylett Section IV: Transduction of the Receptor Signal Chapter 6 Receptors Linked to Ion Channels: Mechanisms of Activation and Block 183 Alasdair J. Gibb Chapter... concentrations of receptors in which the binding sites for A are free and occupied, respectively It may seem odd to refer to receptor concentrations in this context when receptors can often move only in the plane of the membrane (and even then perhaps to no more than a limited extent, as many kinds of receptors are anchored) However, the model can be formulated equally well in terms of the proportions of a population... number of receptors in which the binding sites are free of A and N is their total number Similarly, pAR is given by NAR/N, where NAR is the number of receptors in which the binding site is occupied by A These definitions are used when discussing the action of irreversible antagonists (see Section 1.6.4) 8 Textbook of Receptor Pharmacology, Second Edition KA p + pAR = 1 [A] AR Hence,* pAR = [A] K A +... of a receptor by an agonist This distinction, it is now appreciated, is crucial to the understanding of the action of agonists and partial agonists Indeed all contemporary accounts of receptor activation take as their starting point a mechanism of the following kind:* vacant K A occupied inactive inactive A+R AR E occupied AR * active (1.7) Here, the occupied receptors can exist in two forms, one of. .. Drug Receptor Interactions Chapter 1 Classical Approaches to the Study of Drug Receptor Interactions 3 Donald H. Jenkinson Section II: Molecular Structure of Receptors Chapter 2 Molecular Structure and Function of 7TM G-Protein-Coupled Receptors 81 Thue W. Schwartz and Birgitte Holst Chapter 3 The Structure of Ligand-Gated Ion Channels .111 Jan Egebjerg Chapter 4 Molecular Structure of . York Washington, D.C. TEXTBOOK of RECEPTOR PHARMACOLOGY Second Edition Edited by John C. Foreman, D.Sc., F.R.C.P. Department of Pharmacology University. selective staining of cells by dyes, as 6 Textbook of Receptor Pharmacology, Second Edition well as the remarkably powerful and specific actions of bacterial