Mediators and Drugs in Gastrointestinal Motility II: 2 Endogenous and Exogenous Agents(59 / 2 Handbook of Experimental Pharmacology / Mediators and Drugs in Gastrointestinal Motility)

This volume places more emphasis on endogenous mediators of gut motility than on drugs used to treat patients with deranged motility. In this respect it resembles most other books on gastroenterology, for while only a relatively small number of drugs are really useful for a rational therapy, a tremendous amount of data is available on neural and hormonal factors regulating the motility of the alimentary canal. Moreover, it must be considered that some of the drugs which can routinely be employed to modify deranged motility of the digestive system are represented by pure or slightly modified endogenous compounds (e. g. , cholecystokinin, its C- terminal octapeptide and caerulein), and it is easy to foresee that their number is destined to increase in the near future. Other drugs are simply antagonists of physiological substances acting on specific receptors (e. g. , histamine H -blockers 2 and opioid compounds). The real explosion of research in this field and the extreme specialization often connected with the use of very sophisticated techniques and methodologies would probably have required a larger number of experts to cover some very specific fields from both an anatomical (lower esophageal sphincter, stomach, pylorus, small and large intestine) and a biochemical (hormones, candidate hormones, locally active substances, neurotransmitters etc. ) point of view.

Table of Contents:
1 Endogenous Substances Which Can Affect Gastrointestinal Motility.- General Introduction.- References.- 2a Peptides: Gastrointestinal Hormones.- Gastrin.- A. Introduction.- B. Effects on the Lower Esophageal Sphincter.- I. Excitation.- 1. In Vitro Studies.- 2. In Vivo Studies.- II. Inhibition.- C. Effects on the Stomach.- I. In Vitro Studies.- 1. Experimental Animals.- 2. Humans.- II. In Vivo Studies.- 1. Experimental Animals.- 2. Humans.- D. Effects on the Small and Large Intestine.- I. In Vitro Studies.- II. In Vivo Studies.- 1. Experimental Animals.- 2. Humans.- E. Conclusions.- References.- Cholecystokinin.- A. Introduction.- B. Structure-Activity Relationships.- C. Effects on the Lower Esophageal Sphincter.- D. Effects on the Stomach.- I. In Vivo Studies.- 1. Gastric Emptying.- II. In Vitro Studies.- E. Effects on Small and Large Intestine.- I. In Vivo Studies.- 1. Experimental Animals.- 2. Humans.- II. In Vitro Studies.- F. Conclusions.- References.- Secretin.- A. Introduction.- B. Action on the Lower Esophageal Sphincter.- C. In Vivo Effects on the Stomach.- D. Gastric Emptying.- E. In Vitro Effects on the Stomach.- F. Effects on the Intestine.- G. Conclusions.- References.- Gastric Inhibitory Polypeptide.- A. Introduction.- B. Effects on Gastrointestinal Motility.- I. Lower Esophageal Sphincter.- II. Intragastric Pressure.- III. Intraluminal Pressure.- C. Interactions.- References.- 2b Peptides: Candidate Hormones.- Substance P.- A. Introduction.- B. Structure-Activity Relationships.- C. Action on Gut Motility.- I. In Vitro Studies.- 1. Natural Analogs.- 2. Antagonists.- II. In Vivo Studies.- D. Conclusions.- References.- Motilin.- A. Introduction.- B. Effects on Gastrointestinal Motility.- I. In Vitro Studies.- II. In Vivo Studies.- 1. Action on the Lower Esophageal Sphincter.- 2. Action on the Motility of the Stomach and the Intestine.- C. Conclusions.- References.- Neurotensin.- A. Introduction.- B. Structure-Activity Relationships.- C. Effects on the Gastrointestinal Tract.- I. In Vitro Studies.- II. In Vivo Studies.- References.- Bombesin.- A. Introduction.- B. Effects on the Motility of the Gastrointestinal Tract.- I. In Vitro Studies.- II. In Vivo Studies.- 1. Effects on the Lower Esophageal Sphincter.- 2. Effects on the Stomach.- 3. Effects on the Small and Large Intestine.- C. Conclusions.- References.- 2c Peptides: Pancreatic Hormones.- Glucagon.- A. Introduction.- B. Effects on the Lower Esophageal Sphincter.- C. Effect on the Stomach.- I. In Vivo Studies.- II. In Vitro Studies.- D. Effects on the Small Intestine.- I. Studies in Experimental Animals.- II. Studies in Humans.- E. Effects on the Large Intestine.- F. Conclusions.- References.- Insulin.- A. Introduction.- B. Effects on the Lower Esophageal Sphincter.- C. Effects on the Stomach.- D. Effect on the Small Intestine.- E. Effects on the Large Intestine.- I. In Vitro Studies.- F. Mechanism of Action.- References.- Pancreatic Polypeptide.- A. Introduction.- B. Structure-Activity Relationships.- C. Effect on Gastrointestinal Motility.- References.- 2d Peptides: Other Hormones.- Vasopressin.- A. Introduction.- B. Effects on the Motility of the Gastrointestinal Tract.- References.- Calcitonin.- A. Introduction.- B. Effects on Gastrointestinal Motility.- I. In Vivo Studies.- II. In Vitro Studies.- References.- Coherin.- A. Introduction.- B. Effects of Coherin.- C. Conclusions.- References.- Thyrotropin-Releasing Hormone.- A. Introduction.- B. In Vitro Studies.- C. In Vivo Studies.- References.- 2e Peptides: Locally Active Peptides ("Vasoactive Peptides"1 Endogenous Substances Which Can Affect Gastrointestinal Motility.- General Introduction.- References.- 2a Peptides: Gastrointestinal Hormones.- Gastrin.- A. Introduction.- B. Effects on the Lower Esophageal Sphincter.- I. Excitation.- 1. In Vitro Studies.- 2. In Vivo Studies.- II. Inhibition.- C. Effects on the Stomach.- I. In Vitro Studies.- 1. Experimental Animals.- 2. Humans.- II. In Vivo Studies.- 1. Experimental Animals.- 2. Humans.- D. Effects on the Small and Large Intestine.- I. In Vitro Studies.- II. In Vivo Studies.- 1. Experimental Animals.- 2. Humans.- E. Conclusions.- References.- Cholecystokinin.- A. Introduction.- B. Structure-Activity Relationships.- C. Effects on the Lower Esophageal Sphincter.- D. Effects on the Stomach.- I. In Vivo Studies.- 1. Gastric Emptying.- II. In Vitro Studies.- E. Effects on Small and Large Intestine.- I. In Vivo Studies.- 1. Experimental Animals.- 2. Humans.- II. In Vitro Studies.- F. Conclusions.- References.- Secretin.- A. Introduction.- B. Action on the Lower Esophageal Sphincter.- C. In Vivo Effects on the Stomach.- D. Gastric Emptying.- E. In Vitro Effects on the Stomach.- F. Effects on the Intestine.- G. Conclusions.- References.- Gastric Inhibitory Polypeptide.- A. Introduction.- B. Effects on Gastrointestinal Motility.- I. Lower Esophageal Sphincter.- II. Intragastric Pressure.- III. Intraluminal Pressure.- C. Interactions.- References.- 2b Peptides: Candidate Hormones.- Substance P.- A. Introduction.- B. Structure-Activity Relationships.- C. Action on Gut Motility.- I. In Vitro Studies.- 1. Natural Analogs.- 2. Antagonists.- II. In Vivo Studies.- D. Conclusions.- References.- Motilin.- A. Introduction.- B. Effects on Gastrointestinal Motility.- I. In Vitro Studies.- II. In Vivo Studies.- 1. Action on the Lower Esophageal Sphincter.- 2. Action on the Motility of the Stomach and the Intestine.- C. Conclusions.- References.- Neurotensin.- A. Introduction.- B. Structure-Activity Relationships.- C. Effects on the Gastrointestinal Tract.- I. In Vitro Studies.- II. In Vivo Studies.- References.- Bombesin.- A. Introduction.- B. Effects on the Motility of the Gastrointestinal Tract.- I. In Vitro Studies.- II. In Vivo Studies.- 1. Effects on the Lower Esophageal Sphincter.- 2. Effects on the Stomach.- 3. Effects on the Small and Large Intestine.- C. Conclusions.- References.- 2c Peptides: Pancreatic Hormones.- Glucagon.- A. Introduction.- B. Effects on the Lower Esophageal Sphincter.- C. Effect on the Stomach.- I. In Vivo Studies.- II. In Vitro Studies.- D. Effects on the Small Intestine.- I. Studies in Experimental Animals.- II. Studies in Humans.- E. Effects on the Large Intestine.- F. Conclusions.- References.- Insulin.- A. Introduction.- B. Effects on the Lower Esophageal Sphincter.- C. Effects on the Stomach.- D. Effect on the Small Intestine.- E. Effects on the Large Intestine.- I. In Vitro Studies.- F. Mechanism of Action.- References.- Pancreatic Polypeptide.- A. Introduction.- B. Structure-Activity Relationships.- C. Effect on Gastrointestinal Motility.- References.- 2d Peptides: Other Hormones.- Vasopressin.- A. Introduction.- B. Effects on the Motility of the Gastrointestinal Tract.- References.- Calcitonin.- A. Introduction.- B. Effects on Gastrointestinal Motility.- I. In Vivo Studies.- II. In Vitro Studies.- References.- Coherin.- A. Introduction.- B. Effects of Coherin.- C. Conclusions.- References.- Thyrotropin-Releasing Hormone.- A. Introduction.- B. In Vitro Studies.- C. In Vivo Studies.- References.- 2e Peptides: Locally Active Peptides ("Vasoactive Peptides").- Angiotensin.- A. Introduction.- B. Structure-Activity Relationships.- C. Effects on the Gastrointestinal Tract.- I. In Vitro Studies.- II. In Vivo Studies.- D. Conclusions.- References.- Bradykinin.- A. Introduction.- B. Effects on the Gastrointestinal Tract.- I. In Vitro Studies.- II. In Vivo Studies.- C. Mechanism of Action.- D. Conclusions.- References.- 3 Amines: Histamine.- A. Introduction.- B. Activity on the Lower Esophageal Sphincter.- C. Action on the Stomach.- D. Gastric Emptying.- E. Action on the Intestine.- F. H2-Receptors.- G. Conclusions.- References.- 4 Acidic Lipids: Prostaglandins.- A. Introduction.- B. Occurrence, Formation, Release, and Degradation of Prostanoids.- I. Occurrence.- II. Formation and Release.- III. Degradation.- C. Actions of Prostanoids on the Tone and Reactivity of Isolated Gastrointestinal Muscle.- D. Prostanoids and Gastrointestinal Nerves.- I. Parasympathetic and Noncholinergic Excitatory Nerves.- II. Adrenergic and Nonadrenergic Inhibitory Nerves.- III. Other Possible Nerves and Neurotransmitters.- E. Prostanoid Antagonists and Different Types of Prostanoid Receptors.- F. Prostanoids and Peristalsis In Vitro.- G. Prostanoids and Motility In Vivo.- H. Prostanoids as Factors in Disordered Gastrointestinal Motility.- I. Gastro-Oesophageal Reflux.- II. Gastrointestinal Disturbances.- III. Diarrhoea.- 1. Bacterial Endotoxins.- 2. Cholera Exotoxin.- 3. Irradiation.- 4. Tumours.- 5. Irritable Colon Syndrome.- 6. Food Intolerance.- 7. Idiopathic Intestinal Pseudo-obstruction.- 8. Dysmenorrhoea.- 9. Idiopathic Postural Hypotension.- 10. Treatment of Diarrhoea with Nutmeg.- J. Beneficial Effects of Prostanoids in Disorders of Gastrointestinal Motility.- I. Worm Expulsion.- II. Postoperative Ileus.- III. Laxatives.- K. Conclusions.- References.- 5 Pharmacology of Adrenergic, Cholinergic, and Drugs Acting on Other Receptors in Gastrointestinal Muscle.- A. General Principles.- I. Myogenic Activity of Gastrointestinal Muscle.- II. Nervous Control of Gastrointestinal Muscle.- III. Receptors and Receptor Mechanisms.- B. Drugs Acting on Adrenoceptors.- I. Alpha-Receptors.- II. Beta-Receptors.- III. Possible Distinction Between Beta1- and Beta2-Adrenoceptors.- IV. Dopamine Receptors.- V. Metoclopramide and Domperidone.- 1. Possible Role as Dopamine Antagonists.- 2. Clinical Applications.- C. Cholinergic Receptors in the Gastrointestinal Tract.- I. Muscarinic Receptors.- 1. Molecular Mode of Action of Cholinergic Agonists.- 2. Transmission at Gastrointestinal Neuronal Synapses.- II. Presynaptic Cholinergic Receptors.- III. Nicotinic Receptors.- D. Morphine and Drugs Acting on Opiate Receptors.- I. Endogenous Opiates.- II. Mode of Opiate Action in Guinea-Pig Intestine.- III. A Physiological Role for Endogenous Opiates in Guinea-Pig Intestine.- IV. Mode of Opiate Action in Other Species.- V. Central and Peripheral Sites of Action of Opiate Agonists.- VI. Opiate Receptor Types.- VII. Opiate Agonists Selective for Gut Receptors.- VIII. Clinical Applications of Opiate Antidiarrhoeal Agents.- E. Laxatives and Constipating Agents.- F. Direct and Indirect Actions.- G. Serotonin Receptors and Antagonists.- I. Early Studies.- II. Neuronal Receptors.- III. Muscle Receptors.- H. Histamine Receptors and Antagonists.- I. H1-Receptors.- II. H2-Receptors.- III. Problems of Classification.- J. Projections for the Future.- References.- 6 Hydrophilic Colloids in Colonic Motility.- A. Introduction.- B. The Nature of Stool Bulk and How it is Provided.- I. Water.- II. Bacteria.- III. Fibre.- IV. Gas.- V. Bulking Agents.- C. Actions of Fibre and of Operations on the Colon Muscle in Diverticular Disease.- I. Changes Induced by Operation.- II. Changes Induced by Cereal Fibre.- III. Other Agents.- D. Actions in Other Colonic Diseases.- E. Clinical Application of Fibre and Hydrophilic Colloid Additives.- References.- 7 Motility and Pressure Studies in Clinical Practice.- A. The Esophagus.- I. Motor Activity.- 1. Upper Esophageal Sphincter.- 2. Esophageal Body.- 3. Lower Esophageal Sphincter.- II. Use of Esophageal Manometry in Clinical Practice.- B. The Stomach.- I. Motor Activity.- 1. Gastric Filling.- 2. Mixing and Grinding of Solid Contents.- 3. Gastric Emptying.- II. Gastric Manometry and Studies of Gastric Emptying in Clinical Practice.- C. The Small Intestine.- I. Motor Activity.- II. Manometry of the Small Intestine in Clinical Practice.- D. The Large Bowel.- I. Motor Activity.- 1. Ileocecal Sphincter.- 2. Colon.- 3. Rectoanal Region.- 4. Transit of Large Bowel Contents.- II. Large Bowel Manometry and Transit Time in Clinical Practice.- E. Conclusions.- References.