Beschreibung
More than 70 years have elapsed since U. S. von Euler and I. H. Gaddum dis covered an unidentified depressor substance in the brain and gut. The effects of the powdery extracts were marked as 'P' on the kymograph tracings, and the nondescript name of 'substance P' still carries the breath of this adventurous period. In the 1960s, substance P returned in another disguise, staging as a hypothalamic peptide that causes copious salivary secretion (see chapter by F. Lembeck and I. Donnerer). This time, though, the mysterious substance was tracked down by S. E. Leeman and her collaborators as an undecapeptide, after it had eluded its identification for some 40 years. Substance P turned out to be the mammalian counterpart of a family of peptides which had been extracted from amphibian and nonvertebrate species and which had been given the name 'tachykinins' by V. Erspamer. Soon novel members of this peptide family were discovered, and in mammals substance P was joined by neurokinin A and neu rokinin B. The presence of tachykinins in frog skin as well as in venoms and toxins of microbes and arachnids raises the possibility that these peptides re present an old system of biological weapons that have been transformed to a particular messenger system in mammals.
Autorenportrait
Peter Holzer obtained his Ph.D. in Physiology and Biochemistry from the University of Graz, Austria, in 1978. His academic career included a postdoctoral fellowship at the A.R.C. Institute of Animal Physiology and the M.R.C. Neurochemical Pharmacology Unit at the University of Cambridge, U.K., in 1980. After becoming Reader in Neuropharmacology at the University of Graz in 1985, he was a visiting scientist with the CURE Digestive Diseases Research Center at the University of California Medical School in Los Angeles, U.S.A., in 1989. In 1993 he was promoted to Professor of Neuropharmacology in the Department of Experimental and Clinical Pharmacology at the University of Graz, Austria. In 2000 Dr. Holzer declined to take the chair of Pharmacology and Toxicology at the Department of Pharmacy of the University of Innsbruck, Austria. Dr. Holzer has been holding grants from the Austrian Science Foundation, the Austrian National Bank, the Federal Ministry of Education, Science and Culture of the Republic of Austria and the Zukunftsfonds of the Province of Styria, Austria. His major research interests are in the fields of neuropharmacology, gastrointestinal pharmacology and experimental neurogastroenterology. Particular topics of research include the function of enteric neurons and primary afferent neurons in health and disease, the implication of neuropeptides and neuropeptide receptors in the regulation of gastrointestinal motility, inflammation and ulceration and the development and pharmacological characterization of experimental models with which to study dyspepsia and visceral pain. Dr. Holzer´s publications include more than 170 papers in peer-reviewed international journals. Dr. Holzer has been Chairman of the European Neuropeptide Club 1994 - 1996, Secretary of the IUPHAR Section of Gastrointestinal Pharmacology 1994 - 1998, and President of the Austrian Neuroscience Association 2002 - 2003. Dr. Holzer has been serving on the editorial boards of several premier journals in his field, including Neuroscience, British Journal of Pharmacology, Neurogastroenterology & Motility, Naunyn-Schmiedeberg's Archives of Pharmacology, Regulatory Peptides and Digestion.
Inhalt
Preface.- History of a Pioneering Neuropeptide: Substance P.- The Tachykinin Peptide Family, with Particular Emphasis on Mammalian Tachykinins and Tachykinin Receptor Agonists.- The Histochemistry of Tachykinin Systems in the Brain.- The Nomenclature of Tachykinin Receptors.- The Mechanism and Function of Agonist-Induced Trafficking of Tachykinin Receptors.-Tachykinin NK1 Receptor Antagonists.-Tachykinin NK2 Receptor Antagonists.-Tachykinin NK3 Receptor Antagonists.-Combined Tachykinin NK1, NK2, and NK3 Receptor Antagonists.-Pre-Protachykinin and Tachykinin Receptor Knockout Mice.- Therapeutic Potential of Tachykinin Receptor Antagonists in Depression and Anxiety Disorders.-Role of Tachykinins in Nausea and Emesis.-Substance P (NK1) Receptor Antagonists.- Analgesics or Not?-Role of Tachykinins in Neurogenic Inflammation of the Skin and Other External Surfaces.-Role of Tachykinins in Obstructive Airway Disease.-Role of Tachykinins in the Gastrointestinal Tract.