Beschreibung
The Editorial Board and the Publishers of the Handbook of Experimental Pharmacology wish to express their profound grief at the untimely death of Professor Peter Baker. Aware of his international recognition as an expert on the ubiquitous role of calcium in physiological processes and their pharma cological control, the Board was gratified when Professor Baker accepted its invitation to edit a new Handbook volume on "Calcium in Drug Actions". He went about this task with his usual energy and effectiveness so that, in the few months before his unexpected death, Professor Baker had mustered his distinguished contributors, got them to provide their manuscripts, and seen almost the entire material into the press. This achievement is all the more remarkable when one bears in mind the extraordinary number of his other commitments during the same time; they are mentioned in Sir Alan Hodgkin's preface to this volume. With so many other professional and personal responsibilities upon him, the Board of the Handbook wishes to record its grateful appreciation for the admirable way in which Professor Baker took on and carried out the additional work of bringing this fine book into existence; and the Board wishes it to be dedicated to the memory of Professor Peter Frederick Baker. The Editorial Board: G. V. R. BORN, P. CUATRECASAS, H. HERKEN, A.
Autorenporträt
Inhaltsangabe1 The Multiple Physiological Roles of Calcium: Possible Sites for Pharmacological Intervention.- References.- Calcium Receptors and Calcium Metabolism.- 2 Chemical Factors Determining the Affinity of a Receptor for Calcium.- A. Introduction.- B. Concentrations in Physiological Conditions.- C. Calcium-Proton Competition.- D. The Calcium-Magnesium Problem.- E. Other Metal Ions.- F. Cooperative Interactions.- G. Binding and Conformational Energy.- H. Kinetic Constraints.- J. On-Off Binding Constants.- K. Diffusion of Ions.- I. In Water.- II. Through Membranes.- III. Pumps.- L. Selective Binding to Unstructured Molecules of High Anionic Charge Density.- M. The Function of Neutral Donors.- N. Calmodulin: An Example of a Calcium Trigger.- O. S-100b: An Example of Ion-Ion Cooperativity.- P. A Look at Phosphorylation Regulation.- Q. Conclusion.- References.- 3 Troponin C and Calmodulin as Calcium Receptors: Mode of Action and Sensitivity to Drugs.- A. Introduction.- B. Brief Historical Survey of Ca Receptor Proteins.- C. General Views of TNC and CaM.- D. Ca Binding of TNC and CaM.- E. Ca Binding to TNC in Relation to Tension Development.- F. Ca Binding to CaM and Enzyme Activities.- G. CaM Ligands: Their Pharmacologic and Physiologic Significance.- I. Discovery of CaM-Inhibiting Drugs (CaM Antagonists).- II. CaM Ligands.- H. Concluding Remarks.- References.- 4 Ligand-Binding Sites on Calmodulin.- A. Introduction.- B. Metal Ion-Binding Sites.- I. Calcium.- II. Calcium Probe Cations.- III. Other Metal Ions.- C. Binding of Drugs.- I. Trifluoperazine.- II. Calmodulin Antagonists.- III. Calcium Antagonists.- D. Binding of Peptides.- I. Structural Requirements.- II. Localization of Binding Sites.- E. Interactions with Target Proteins.- I. Chemical Modifications and Affinity Labeling.- II. Activation and Binding with Calmodulin Fragments.- III. Calmodulin-Binding Domains.- F. Epilogue.- References.- 5 Calcium Channels as Drug Receptors.- A. Introduction.- B. Calcium as a Biological Signalling Mechanism and the Role of Calcium Channels in Maintaining Its Homeostasis.- C. How Many Types of Calcium Channels Exist?.- D. Electrophysiological Properties of the Calcium Channel.- E. Physiological Modulation of Calcium Channel Function.- F. Calcium Antagonists.- G. The 1,4-Dihydropyridine Receptor.- H. Calcium Agonists.- J. Summary and Conclusions.- References.- 6 The Chemistry of Calcium Channel Agonists and Antagonists.- A. Introduction.- B. Structure-Function Studies.- C. Binding Sites for Ca2 + Channel Ligands.- D. Ca2+ Channel Binding Sites: Relationship to Ca2+ Channel Function.- E. Relationship of Structural and Functional Studies: A Prospective.- I. Different Categories of Ca2+ Channels.- II. State-Dependent Interactions with Ca2 + Channels.- III. Pathologic State of Tissue.- References.- 7 The Apamin-Sensitive Ca2+-Dependent K+ Channel: Molecular Properties, Differentiation, Involvement in Muscle Disease, and Endogenous Ligands in Mammalian Brain.- A. Apamin, Its Structure and Its Active Site.- B. Apamin Blocks Ca2+-Dependent K+ Channels.- C. The Apamin-Sensitive Ca2+-Dependent K+ Channel is Only One of Several Types of Ca2+-Dependent K+ Channels.- D. Biochemical Properties of the Apamin-Binding Component of the Ca2+-Dependent K+ Conductance.- E. Apamin as a Tool to Purify the Apamin-Sensitive Ca2+-Dependent K+ Channel and to Determine Its Molecular Weight and Its Polypeptide Composition.- F. PCI2 Pheochromocytoma Cells Hyperproduce the Apamin Receptor and Permit an Analysis of the Internal Ca2+ Concentration Dependence of the Apamin-Sensitive Ca2 + Channel.- G. Autoradiographic Localization of Apamin-Sensitive Ca2+-Dependent K+ Channels in Rat Brain.- H. Developmental Properties of the Ca2+-Dependent K+ Channel in Mammalian Skeletal Muscle and the All-or-None Role of Innervation.- I. Expression of the Apamin Receptor in Muscles of Patients with Myotonic Muscular Dystrophy.- J. An Endogenous Apamin-Like Factor Modulating Ca2+-Dependent K+
