Bibliographic Information

Pharmacology of smooth muscle

contributors, M.L. Cohen ... [et al.] ; editors, Laszló Szekeres and Julius Gy. Papp

(Handbook of experimental pharmacology, v.111)

Springer-Verlag, 1994

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Includes bibliographical references and index

Description and Table of Contents

Description

A comprehensive and systematic survey of the present knowledge of the structure and physiological functions of smooth muscle and its response to endogenous substances and pharmacological agents. The latter includes findings on different organ systems containing smooth muscle - with the exception of the vascular system which, owing to the great amount of new knowledge accumulated in this area in recent years, is treated in a special chapter. In this connection the effect of antihypertensive agents and drugs affecting the coronary and cerebrovascular smooth muscle is also covered. For all those wishing to gain a deeper insight into smooth muscle pharmacology.

Table of Contents

Section I: General Aspects.- 1 Structure of Smooth Muscles.- A. Introduction.- B. Smooth Muscle Cells.- I. Cell Size.- II. Cell Membrane.- III. Caveolae.- IV. Cell Junctions.- V. Dense Bands.- VI. Sarcoplasmic Reticulum.- VII. Filaments.- 1. Myosin Filaments.- 2. Actin Filaments.- 3. Dense Bodies.- 4. Intermediate Filaments.- C. Smooth Muscle as a Tissue.- I. Non-muscle Cells.- II. Extracellular Materials.- D. Changeable Structure of Smooth Muscles.- I. Contraction.- II. Development.- III. Hypertrophy.- References.- 2 Ionic Channels in Smooth Muscle.- A. Introduction.- B. Voltage-Operated Ca2+ Channel.- I- Type.- II. Ionic Selectivity.- III. Inactivation.- IV. Blocking Agents.- V. Intracellular ATP.- VI. pH Effect.- C. K+ Channel.- I. Ca2+-Activated K+ Channel.- II. ATP-Regulated Channel.- III. Fast-Inactivating K+(Kfi) Channel.- IV. Delayed Rectifying K+(Kdr) Channel.- V. Time-Independent K+(Kti) Channel.- VI. Inward-Rectifying K+(Kir) Channel.- D. Na+ Channel.- E. Cl- Channel.- I. Ca-Activated CP Channel.- II. Voltage-Dependent Channel.- References.- 3 Excitation-Contraction Coupling Mechanisms in Visceral Smooth Muscle Cells.- A. Introduction.- B. General Features of the Sarcolemmal Membrane in Relation to the Influx of Calcium.- I. Action Potentials Recorded by Microelectrode Methods.- 1. Action Potentials.- 2. Nerve-Mediated Responses.- II. Features of the Voltage-Dependent Ca Channel in Visceral Smooth Muscle Membranes Measured Using the Voltage- and Patch-Clamp Procedures.- III. Factors Modifying the Activity of the Voltage-Dependent Ca Channel.- 1. Ca Antagonists and Agonists.- 2. Dihydropyridine-Binding Protein (Ca Channel).- 3. K Channel Modifying Drugs.- 4. Endothelial Cell Releasing Factors.- IV. Receptor-Operated Ion Channel.- 1. General Features of the Receptor Structure.- 2. Neurotransmitter-Induced Changes in the Membrane Potential.- 3. Activation of the Receptor-Operated Ion Channel.- V. Mutual Relationship Between the Voltage-Dependent and Receptor-Activated Ion Channels.- VI. Factors Modifying the Mechanical Responses with No Change in the Ca Concentration.- VII. Ca Influx Induced by a Reversed Na-Ca Exchange Diffusion Mechanism.- VIII. Ca Influx Induced by Stretch.- C. Sarcoplasmic Reticulum as a Cytosolic Calcium Regulator in Visceral Smooth Muscles.- I. Release of Ca from the SR as Estimated from the Ca Transient and Contraction.- II. Role of the SR in Relation to the Release of Ca.- 1. Caffeine-Induced and IP3-Induced Ca Release.- 2. Release of Ca from the SR Deduced from the Ca-Dependent K Current.- 3. Receptor Proteins of the Ca-Release Channel.- D. Actions of Calcium on Contractile Proteins.- I. Ca-Binding Proteins.- II. Myosin Phosphorylation Model for Smooth Muscle Contraction.- III. Actin-Regulating Mechanisms in Smooth Muscle.- 1. Caldesmon.- 2. Calponin.- IV. Roles of Calcium as Estimated from Mechanical Responses.- V. Pharmacology of Ca-Dependent Protein Phosphorylation.- E. Conclusion.- References.- Section II: Endogenous Substances and Smooth Muscle.- 4 Eicosanoids and Smooth Muscle Function.- A. Introduction.- B. Cellular Aspects of Formation and Action of Eicosanoids in Smooth Muscle Cells.- I. Control of Local Eicosanoids Levels.- 1. Phospholipases and Arachidonic Acid Liberation.- 2. Control of Enzyme Mass.- 3. Circulating Hormones and Chemical Messengers.- II. Additional Sources of Eicosanoids for Smooth Muscle.- 1. Endothelial/Epithelial Cells.- 2. Platelets.- 3. Leukocytes.- III. Signal Transduction Pathways in Smooth Muscle Cells.- 1. Eicosanoid Receptors.- 2. G Proteins.- 3. Phosphoinositol Metabolism, Protein Kinase C, and Cytosolic Ca2+.- 4. Cyclic Nucleotide Related Pathways.- 5. Ionic Channels.- C. Eicosanoids and Smooth Muscle Function.- I. Cyclooxygenase Products.- 1. Prostaglandin Endoperoxides.- 2. Prostaglandin D2.- 3. Prostaglandin E2.- 4. Prostaglandin F2?.- 5. Prostaglandin I2.- 6. Thromboxane A2.- II. Leukotriene Pathways.- 1. Leukotriene B4.- 2. Cysteinyl Leukotrienes.- III. Other Lipoxygenase Products.- 1. 5-Hydro(pero)xyeicosatetraenoic Acid.- 2. 12-Hydro(pero)xyeicosatetraenoic Acid.- 3. 15-Hydro(pero)xyeicosatetraenoic Acid.- 4. Lipoxins.- 5. Hepoxilins.- IV. Monooxygenase Pathways.- D. Eicosanoids and Smooth Muscle Dysfunction.- I. Smooth Muscle Cell Proliferation.- II. Smooth Muscle Tone in Pathologic Situations.- 1. Arterial Vasospasm.- 2. Bronchospasm.- E. Summary and Conclusions.- References.- 5 Angiotensin, the Kinins, and Smooth Muscle.- A. Introduction.- B. Renin-Angiotensin System.- I. Effects of Angiotensin on the Cardiovascular System and on Smooth Muscles.- II. Receptor Characterization: Pharmacological Assays.- III. Receptor Characterization by the Binding.- IV. Cloning and Expression of the Angiotensin Receptor.- V. Mechanism of Action of Angiotensin: Second Messenger(s).- C. Kallikrein-Kinin System.- I. Mechanism of Action of Bradykinin: Second Messenger(s).- References.- 6 Effect of Histamine on Smooth Muscle.- A. Introduction.- B. The Gastrointestinal Tract.- I. Activity of the Esophagus.- II. Action on the Stomach.- III. Action on the Intestine.- IV. Action on the Gallbladder.- V. Conclusion.- C. The Genitourinary Tract.- I. Action on the Ureter, Bladder and Penile Tissue.- II. Action on the Uterus.- D. The Cardiovascular System.- I. Overview and Historical Background.- II. Aorta.- III. Coronary Vessels.- IV. Cerebral Vessels.- V. Pulmonary Vessels.- VI. Portal, Mesenteric and Renal Vessels.- VII. Vascular Physiopathology.- E. Pulmonary Tract.- I. Introductory Notes.- II. Effects of Histamine on Airway Smooth Muscle.- F. Concluding Remarks.- References.- 7 Angiohypotensin.- A. Introduction.- B. Angiohypotensin in Human and Mammalian Sera.- C. Inhibition by Angiohypotensin of the Release of Noradrenaline to Field Stimulation in Vascular Smooth Muscle.- D. Angiohypotensin in Pig and Bovine Liver.- E. Hypotensive Effect of Moderately Purified Angiohypotensin Preparations in Anaesthetized Animals.- F. Blood Pressure Reducing Effect of Highly Purified Angiohypotensin Preparations in Anaesthetized Spontaneous Hypertensive Rat (SHR Strain).- G. Blood Pressure Reducing Effect of Highly Purified Angiohypotensin Preparations in Freely Moving Awake, Spontaneously Hypertensive Rats and in Their Normotensive Control Peers.- H. Working Hypothesis of Angiohypotensin As a Major Regulator of Peripheral Vascular Resistance.- I. Summary and Conclusion.- References.- 8 Neuropeptides (Neurokinins, Bombesin, Neurotensin, Cholecystokinins, Opioids) and Smooth Muscle.- A. Introduction.- I. Receptors for Neuropeptides.- II. Smooth Muscle as Target for Neuropeptides.- III. Neuropeptide Receptors in Smooth Muscle.- IV. Neuropeptide Metabolism.- B. Substance P and Related Neurokinins.- I. Biological Activity of Neurokinins In Vivo.- II. Neurokinin-Receptor Activity in Isolated Smooth Muscles In Vitro.- III. Mechanisms of Action of Neurokinins: Mediators and Second Messengers.- C. Gastrin-Releasing Peptides and Neuromedins B.- I. Biological Activity of Bombesin-Related Peptides In Vivo and In Vitro.- II. Second Messengers of Bombesin Receptors.- D. Neurotensin.- I. Biological Activity of Neurotensin In Vivo.- II. Pharmacological Effects of Neurotensin In Vitro: Receptor Characterization.- III. Mechanism of Action of Neurotensin and Second Messengers.- E. Cholecystokinin.- I. Biological Activity of Cholecystokinin In Vivo.- II. Activity of Cholecystokinin In Vitro.- III. Mechanism of Action of CCK and Second Messengers.- F. Opioids.- I. Biological Activity of Opioids In Vivo.- II. Effects of Opioids In Vitro.- III. Characterization of Opioid Receptors by Endogenous Agonists, Antagonists and Selective Analogues.- IV. Mechanism of Action of Opioids on Smooth Muscle and Second Messengers Involved.- References.- 9 Serotonin and Smooth Muscle.- A. Introduction.- B. History.- C. Serotonin Receptor Identification and Classification.- D. Vascular Smooth Muscle.- I. Source of Serotonin.- II. General Comments on Vascular Responses.- III. Neuronal Receptors in Vascular Smooth Muscle.- IV. Serotonin Receptors Responsible for Vascular Smooth Muscle Contraction.- V. Vascular Relaxation.- E. Gastrointestinal Smooth Muscle.- I. Source of Serotonin.- II. General Comments on Gastrointestinal Responses.- III. Neuronal Receptors in Gastrointestinal Smooth Muscle.- IV. Esophageal Smooth Muscle.- V. Gastric Smooth Muscle.- VI. Ileal Smooth Muscle.- VII. Colonic Smooth Muscle.- F. Pulmonary Smooth Muscle.- G. Genitourinary Smooth Muscle.- I. Vas Deferens.- II. Bladder.- III. Prostate.- IV. Penile Smooth Muscle.- V. Uterine Smooth Muscle.- H. Summary.- References.- Section III: Pharmacological Agents and Smooth Muscle.- 10 Excitation-Contraction Coupling in Gastrointestinal Smooth Muscles.- A. Introduction.- B. Mechanisms of Electrical Behavior of GI Smooth Muscles.- I. Major Ionic Currents Identified in GI Smooth Muscles.- 1. Properties of Voltage-Dependent Ca2+ Currents.- 2. Properties of K+ Currents.- 3. Properties of Chloride Currents.- 4. Properties of Sodium Currents.- II. Contribution of Ionic Channels to Electrical Activity and Electromechanical Coupling.- 1. Pacemaker Currents.- C. Regulation of Ionic Currents by Agonists.- I. Regulation of Currents by Muscarinic Stimulation.- 1. Nonselective Cation Currents.- 2. Regulation of Calcium Currents.- 3. Regulation of Outward Currents.- II. Regulation of Currents by Adrenergic Stimulation.- III. Regulation of Currents by Nitrosovasodilators.- IV. Regulation of Currents by Peptides.- V. Regulation of Currents by K+ Channel Agonists.- D. Coupling Between Electrical Excitation and Contraction.- I. Relationship Between Ca2+ Current and [Ca2+]i.- II. Regulation of Ca2+ Influx by [Ca2+]i.- III. Relationship Between Electrical Activity and [Ca2+]i in Muscle Strips.- IV. Ca2+ and Metabolism.- V. Relationship Between [Ca2+]i and Force.- E. Role of Phosphatidyl Inositol Turnover.- I. Regulation Via IP3.- II. Role of Activators of Protein Kinase C.- F. Regulation of the Contractile Apparatus by Cyclic Nucleotides.- G. Summary.- References.- 11 Airway Smooth Muscle.- A. Introduction.- B. Contractile Mechanisms.- I. Receptor-Operated Contraction.- II. Initiation.- III. Maintenance.- IV. Depolarisation-Induced Contraction.- V. Sources of Calcium Utilised During Contraction.- C. Relaxant Mechanisms.- I. Elevation of Cyclic AMP.- II. Elevation of Cyclic GMP.- III. Breakdown of cAMP and cGMP.- D. Calcium Removal Mechanisms.- I. Calcium Efflux Pump.- II. Sodium-Calcium Exchange.- III. Intracellular Calcium Removal Mechanisms.- IV. Calcium During Relaxation.- E. Effect of Drugs on Airway Smooth Muscle Function.- I. Drugs Acting Via Smooth Muscle Receptors.- 1. Adrenergic Agents.- 2. Muscarinic Agents.- 3. NANC System Neurotransmitters.- 4. Agents Acting on Guanylate Cyclase.- 5. Inflammatory Mediators/Epithelial Products.- II. Drugs Acting on Post-receptor Mechanisms.- 1. Phosphodiesterase Inhibitors.- 2. Miscellaneous.- III. Drugs Acting on Cell Membrane Ion Transport.- 1. Calcium Channel Antagonists.- 2. Potassium Channel Activators.- 3. Others.- F. Conclusion.- References.- 12 Uterine Smooth Muscle: Electrophysiology and Pharmacology.- A. Introduction.- B. Electrical Activity of Myometrium.- I. Relationship Between Membrane Potential and Contraction.- II. Ion Channels: Identification and Modulation.- 1. Voltage-Gated Calcium Channels.- 2. Voltage-Gated Sodium Channels.- 3. Ligand-Gated Nonspecific Channels.- 4. Potassium Channels.- 5. Other Channels.- C. Contractile Activity of Myometrium.- I. Calcium Entry from the Extracellular Medium.- II. Calcium Release from the Intracellular Calcium Store.- 1. Agonist Effects on the Intracellular Calcium Store.- 2. Characteristics of the Intracellular Calcium Store.- 3. Relaxant Effects of Caffeine in Myometrium.- III. Phosphoinositide Cycle.- 1. Action of InsP3.- 2. Action of Phorbol Esters.- D. Summary and Conclusions.- References.- 13 Effect of Potassium Channel Modulating Drugs on Isolated Smooth Muscle.- A. Introduction.- I. Modulation of Potassium Channels: General Principles.- II. Mechanical Consequences of K-Channel Modulation.- 1. Plasmalemmal Effects.- 2. Other Intracellular Effects.- B. K-Channels in Smooth Muscle.- I. Voltage-Sensitive Channels.- 1. General Features of Activation and Inactivation.- 2. Channel Substructure.- 3. Voltage-Sensitive K-Channel Subtypes.- II. Calcium-Sensitive K-Channels.- 1. BKCa.- 2. SKCa.- 3. IKCa.- 4. KCa(o).- III. ATP-Sensitive K-Channels.- C. Modulators of Smooth Muscle K-Channels.- I. Synthetic K-Channel Openers.- 1. Chemical Classification.- 2. Effects on Smooth Muscle In Vitro.- 3. Effects on K-Channels.- II. Endogenous K-Channel Openers.- 1. Adenosine.- 2. Calcitonin Gene-Related Peptide.- 3. Endothelium-Derived Hyperpolarising Factor.- 4. Fatty Acids.- 5. Prostacyclin.- 6. Vasoactive Intestinal Polypeptide.- 7. Adrenoceptor Agonists.- 8. Endogenous Relaxants: Involvement of K-Channels.- III. K-Channel Inhibitors.- 1. Inorganic Cations.- 2. Aminopyridines, TEA.- 3. Class III Antiarrhythmic Agents.- 4. Imidazoline-Guanidino Receptor Site Ligands.- 5. Toxins.- 6. Hypoglycaemic Agents.- 7. Calmodulin Antagonists.- D. Selectivity of Action.- References.- 14 Smooth Muscle of the Male Reproductive Tract.- A. Introduction.- B. Extrinsic Nerves.- C. External Reproductive Organs.- I. General Properties of the Smooth Muscle.- II. Adrenergic Mechanisms.- 1. ?-Adrenoceptors.- 2. ?-Adrenoceptors.- III. Cholinergic Mechanisms.- 1. Muscarinic Effects.- 2. Nicotinic Effects.- IV. Peptides.- 1. VIP.- V. l-Arginine Nitric Oxide Synthase Pathway.- 1. Background Constituted by the Inhibitory Factor Extracted from the Bovine Retractor Penis Muscle.- 2. Nitric Oxide Synthase and the Use of Its Inhibitors.- 3. Physiological Significance.- D. Internal Accessory Reproductive Organs.- I. General Properties of the Smooth Muscle.- II. Adrenergic Mechanisms.- 1. ?-Adrenoceptors.- 2. ?-Adrenoceptors and Their Significance.- III. Cholinergic Mechanisms.- 1. Excitatory Muscarinic Effects.- 2. Inhibitory Muscarinic Effects.- 3. Physiological Significance of Cholinergic Nerves.- IV. Peptides.- V. Cotransmission.- E. Concluding Remarks.- References.- 15 Urinary Tract.- A. Introduction.- B. Species Differences.- C. Anatomy and Physiology.- D. Innervation and Effects of Drugs.- I. Hypogastric Nerve.- II. Pelvic Nerve.- III. Modulators.- 1. Transmitters.- 2. Hormones.- 3. Prostaglandins and Others.- E. Smooth Muscle.- I. Membrane Excitability.- II. Calcium Channels.- III. Potassium Channels.- IV. Contractile Mechanism.- F. Clinical Considerations.- G. Conclusions.- References.- Section IV: Vascular System.- 16 Molecular Mechanisms of Action of Antihypertensive Agents, Ca-Antagonists and K-Channel Openers on Vascular Smooth Muscle.- A. Introduction.- B. Classification of Ca-Antagonists and K-Channel Openers.- C. Ion Channels Distributed in Vascular Smooth Muscle Cells.- I. Ca Channels.- II. Na Channels.- III. K Channels.- 1. Ca-Dependent K Channels.- 2. ATP-Sensitive K Channels.- 3. A-Type Channels.- 4. Delayed K Channels.- 5. Other K Channels.- IV. Non-selective Cation Channels.- V. Cl Channels.- D. Actions of Ca-Antagonists on the Membrane of Smooth Muscle Cells.- E. Molecular Mechanisms Underlying the Actions of Ca-Antagonists on the Ca Channel.- F. Heterogeneity of the K Channel Targeted by K-Channel Openers.- G. Properties and Gating Mechanisms of the ATP-Sensitive K Channel.- I. Inhibition by ATP and Its Analogues.- II. Reactivation by ATP and Its Analogues.- H. Mechanisms of Action of K-Channel Openers on the ATP-Sensitive K Channel.- I. Conclusion.- References.- 17 Drug Effects on the Smooth Muscle of the Coronary System Under Physiological and Pathological Conditions.- A. Introduction.- B. Function of the Coronary System.- C. Changes Due to Pathological Conditions.- D. Effect of Drugs on the Coronary System.- References.- 18 Drugs Affecting the Cerebrovascular Smooth Muscle.- A. Introduction.- B. Endothelium-Dependent Vasorelaxation.- I. Endothelium-Derived Relaxing Factor.- II. EDRF and Cerebral Blood Vessels.- III. Pathophysiology.- C. Endothelium-Dependent Vasoconstriction.- I. Endothelium-Derived Constricting Factors.- II. EDCFs and Cerebral Blood Vessels.- III. Endothelin in Cerebral Blood Vessels.- IV. Unidentified EDCF in Cerebral Blood Vessels.- V. Pathophysiology.- D. Cerebrovascularly Acting Drugs.- I. Adrenoceptor Antagonists and Agonists.- II. Acetylcholine.- III. 5-HT and Its Receptor Antagonists.- IV. Neuropeptides.- 1. Neuropeptide Y.- 2. Vasoactive Intestinal Polypeptide.- 3. Tachykinins.- 4. Calcitonin Gene-Related Peptide.- 5. Miscellaneous Peptides.- V. Adenosine, Adenine Nucleotides and Related Drugs.- VI. Histamine and Its Antagonists.- VII. Thrombin.- VIII. Ca Antagonists.- IX. K-Channel Openers.- X. Prostanoids and Related Drugs.- References.- 19 Altered Responsiveness of Vascular Smooth Muscle to Drugs in Diabetes.- A. Introduction.- I. Atherosclerosis in Diabetes.- II. Microangiopathy in Diabetes.- III. Diabetic Vascular Smooth Muscle.- B. Altered Vascular Response in Diabetes.- I. History.- II. Localization.- III. Pathomechanism.- 1. Adrenergic Receptor.- 2. Vasoactive Mediators.- IV. Clinical Consequences.- C. Summary.- References.

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