Biomedical Engineering Reference
In-Depth Information
12
Receptors: Structure,
Function, and Pharmacology
Hans Bräuner-Osborne
CONTENTS
12.1 Introduction ......................................................................................................................... 189
12.1.1 Synaptic Processes and Mechanisms..................................................................... 190
12.2 Receptor Structure and Function ........................................................................................ 192
12.2.1 G Protein-Coupled Receptors ................................................................................ 192
12.2.2 Ligand-Gated Ion Channel Receptors ................................................................... 195
12.2.2.1 The Cys-Loop Receptor Family............................................................. 195
12.2.2.2 The Ionotropic Glutamate Receptor Family .......................................... 196
12.2.3 Tyrosine Kinase Receptors .................................................................................... 197
12.2.4 Nuclear Receptors .................................................................................................. 198
12.3 Receptor Pharmacology ...................................................................................................... 199
12.3.1 Recombinant versus
in Situ
Assays ....................................................................... 199
12.3.2 Binding versus Functional Assays ......................................................................... 199
12.3.3 Partial and Full Agonists .......................................................................................200
12.3.4 Antagonists ............................................................................................................200
12.3.5 Constitutively Active Receptors and Inverse Agonism.......................................... 202
12.3.6 Allosteric Modulators ............................................................................................ 203
12.3.6.1 Negative Allosteric Modulators (Noncompetitive Antagonists) ............ 203
12.3.6.2 Positive Allosteric Modulators ............................................................... 203
12.4 Concluding Remarks...........................................................................................................204
Further Readings ............................................................................................................................204
12.1 INTRODUCTION
Communication between cells is mediated by compounds such as neurotransmitters and hormones,
which, upon release, will activate receptors in the target cells. This communication is of pivotal
importance for many physiological functions and dysfunction in cell communication pathways
often have severe consequences. Many diseases are caused by dysfunction in the pathways and in
these cases, drugs designed to act at the receptors have benei cial effects. Thus, receptors are very
important drug targets.
The i rst receptors were cloned in the mid-1980s and since then hundreds of receptor genes have
been identii ed. Based on the sequence of the human genome it is currently estimated that more
than 1000 human receptors exist. Almost all receptors are heterogeneous, meaning that several
receptor subtypes are activated by the same signaling molecule. One such example is the excitatory
neurotransmitter glutamate. As shown in Figure 12.1, the amino acid sequence of the glutamate
receptors vary and the receptors form subgroups, which, as will be discussed in Chapter 15, share
pharmacology.
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