ABSTRACT
Early in the 1970s, an intense research on neuropeptides was initiated, fueled by the following seminal discoveries: (1) most of the hypothalamic-releasing and -inhibiting hormones were shown to be peptides by Roger Guillemin and Andrew Schally’s groups; (2) substance P, though discovered in 1931 by Ulf von Euler and John Gaddum, was chemically identied as an 11-amino acid peptide by Susan Leeman and coworkers only in 1971; (3) the rst endogenous ligands for the morphine receptors were identied as two pentapeptides, leucine-and methionine-enkephalin
1.1 Neuropeptide Research-The Beginnings .......................................................1 1.2 Neuropeptides-Transmitters or Trophic Factors, or Both?.............................2 1.3 How Neuropeptides Have Been Discovered .....................................................2 1.4 How Neuropeptides Are Monitored .................................................................7 1.5 What Makes Neuropeptides Unique as Messenger Molecules? .......................8 1.6 Plasticity of Neuropeptide Expression ..............................................................9 1.7 Neuropeptide Receptors ................................................................................. 10 1.8 Neuropeptide Drugs and Pharmacology ........................................................ 11 1.9 Why Are Neuropeptide Receptors Attractive Targets for Drug
Development? ................................................................................................. 11 1.10 Neuropeptide Systems as Targets for Treatment of Neuropathic Pains ......... 12 1.11 Galanin as a Pain Transmitter ....................................................................... 12 1.12 Galanin as a Trophic Molecule ...................................................................... 14 1.13 Concluding Remarks ...................................................................................... 15 Acknowledgments .................................................................................................... 15 References ................................................................................................................ 15
by John Hughes, Hans Kosterlitz, and coworkers; (4) the gut peptide cholecystokinin (CCK), discovered by Viktor Mutt and Erik Jorpes, and the vasodilatory peptide vasoactive intestinal polypeptide (VIP), isolated by Sami Said and Viktor Mutt, were found in the brain; and last but not least (5) David de Wied and coworkers’ pioneering behavioral work, showing interesting central effects of peripherally administered peptides like vasopressin and oxytocin, opening up the idea that these posterior pituitary hormones can bypass the blood-brain barrier (BBB) and act on receptors in the brain, further corroborated by Abba Kastin and coworkers. Subsequently, the rate of discovery of neuropeptides accelerated, and during the rst decade of the third millennium new members of the family have been added. Thus, we now know of several hundred neuropeptides, many of them belonging to chemically, or functionally, distinct families. Clearly, neuropeptides have emerged by far as the largest group of messenger molecules in the nervous system, as recently reviewed by Burbach (2010) (Table 1.1).
