Advances in General and Cellular Pharmacology: Volume 1

ISBN-13: 9781461582007 / Angielski / Miękka / 2012 / 252 str.

Toshio Narahashi; C. Paul Bianchi

Opis

Knowledge of the mechanism of action of drugs at cellular, subcellular, or molecular levels is of vital importance not only in giving the basis of inter pretation of the systemic action of drugs but also in improving existing drugs; in designing new forms of drugs; and in giving the basis of therapeutic applications. Classical pharmacology, concerning the action of drugs at integrated levels, does not necessarily give sufficient information as to the mechanism of action of drugs. A variety of sophisticated concepts utilizing the methods of physics, chemistry, biophysics, biochemistry, and physiology must be synthesized to understand the mechanism of action. Only since the last decade, however, have these techniques been fully applied to pharma cological investigations. It is of utmost importance to realize that a new dimension of pharmacological research has indeed emerged as a result of such a multidisciplinary approach; this approach is encompassed in general and cellular pharmacology. Such recent studies of drug actions have led to a number of important findings. Certain chemicals and drugs were found to possess highly specific actions on cellular functions, so that they are widely being used as powerful tools for the study of a variety of physiological and pharmacological prob lems. Our knowledge of the cellular mechanisms of drug action has provided the basis for interpreting the systemic effects of the drugs and insight into the molecular mechanism involved."

Spis treści

1 Cardiac Cellular Pharmacology: Automaticity in Cardiac Muscle—Its Alteration by Physical and Chemical Influences.- I. Automaticity in Heart Muscle.- II. Characteristics of the “Resting” Membrane in Cardiac Cells.- A. Membrane Cable Properties.- B. The Basis of Resting Transmembrane Voltage.- III. Membrane Currents which Underlie Spontaneous Phase 4 Depolarization in Automatic Cardiac Cells.- A. Outward Currents.- B. Inward Currents.- IV. Modification of Automaticity by Physical and Chemical Agents.- A. Normal Ionic Constituents and Neurohumors.- B. Physical Factors.- C. Exogenous Chemical Factors.- V. Summary.- References.- 2 Actions of Opiates and Their Antagonists on Cholinergic Transmission in the Guinea Pig Ileum.- I. Introduction.- II. Mechanism of Contractions Induced by Electrical Stimulation.- III. Procedure for Setting Up the Ileum.- IV. Determination of Opiate Potency.- V. Site of Blocking Action of Drugs.- VI. Activities of Opiates and Antagonists on the Ileum.- VII. Actions of Inhibitors of Prostaglandin Synthesis.- VIII. Mechanism of Opiate Effects on Cholinergic Transmission: Relation to the Prostaglandin System.- References.- 3 Pharmacology of Heart Cells During Ontogenesis.- I. Introduction.- II. Experimental Methods.- A. Isolated Cardiac Tissues and Heart Cells in Culture.- B. Measurements of Cellular Activity.- III. Cardiac Development.- A. General Morphologic Features.- B. Innervation and Histochemical Observations.- C. Ion Content and Distribution.- D. Electrical Properties of Cardiac Cells.- E. Changes in Heart Rate During Development.- IV. Modification of Electrical and Mechanical Activity of Embryo Hearts Produced by Drugs.- A. Cholinergic Transmission and Cholinergic Drugs.- B. Adrenergic Transmission and Adrenergic Drugs.- C. Nicotine and Tyramine.- D. Tetrodotoxin.- E. Digitalis Glycosides.- V. Summary.- References.- 4 Analysis of Dose—Response Relationships.- I. Some Comments on General Pharmacology.- II. Empirical Examination of Dose-Response Curves.- A. Classification of Dose-Response Curves.- B. Classification of Antagonists.- C. Empirical Indices.- III. Kinetic Analysis of Dose-Response Curves.- A. Models.- B. Estimation of Dissociation Constants.- C. Statistical Aspects.- IV. Mechanistic Analysis of the Dose-Response Relationship.- A. Access.- B. Reaction with the Receptor.- C. Actuation.- V. Summary.- References.- 5 Cellular Pharmacology of Ganglionic Transmission.- I. General Characteristics of Autonomic Ganglia.- A. Morphological Aspects.- B. Functional Aspects.- II. Postsynaptic Receptor Sites.- A. Excitatory Cholinoceptive Sites.- B. Excitatory Noncholinoceptive Site.- C. Inhibitory Adrenoceptive Site.- III. Presynaptic Receptor Sites.- A. Cholinoceptive Site.- B. Adrenoceptive Site.- IV. Transmitter Liberation.- A. Quantal Liberation of ACh from Preganglionic Nerve Terminals.- B. Facilitation and Depression of Transmitter Liberation.- C. Effects of Ganglionic Blocking Agents.- V. Some Specific Physiopharmacologic Characteristics of Postsynaptic Neuron Membrane.- A. Effects of Alkaline Earth Cations.- B. Effects of Caffeine.- C. Hyperpolarization Owing to Activity of an Electrogenic Pump.- References.