Neuropeptides.{IM)
`v. 33, no. 2-3 (Apr-Jua 2004)
`General Col!ec!ion
`W1 NE337SL
`2oo<t-ne-12
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`r
`
`PROPERTY OF THE C L.,
`NATIONAL i7
`LIBRARYOF(Z)
`MEDICINE
`---·
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`0
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`..j"
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`~ 2004 VOLUME 38 ISSUES 2 AND 3
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`~ ~ IND
`·~ S074667
`
`

`

`Neuropeptides
`
`Editorial Board
`
`Editor in Chief
`Jacqueline N. Crawley, USA
`
`Editorial Board Members
`Susan D. Brain, UK
`Douglas Brenneman, USA
`Donald R. Gehlert, USA
`Lisa H. Gold, USA
`Markus Heilig, Sweden
`Herbert Herzog, Australia
`Tomas Hokfelt, Sweden
`John Hughes, UK
`Joseph P. Huston, Germany
`Leslie Iversen, UK
`George Koob, USA
`Michael J. Kuhar, USA
`Stafford McLean, USA
`Elliott J. Mufson, USA
`Charles B. Nemeroff, USA
`John Quinn, UK
`Remi Quirion, Canada
`Alfredo Ribeiro-da-Silva, Canada
`Bernard P. Roques, France
`William Rostene, France
`Kim Seroogy, USA
`Gerard Smith, USA
`Stanley J. Watson, USA
`Zsuzsanna Wiesenfeld-Hallin, Sweden
`
`ELSEVIER
`
`

`

`Aims and Scope
`The aim of Neuropeptit!es is the rapid publication of original research
`and review articles, dealing with the structure, distribution, actions and
`functions of peptides in the central and peripheral nervous systems.
`The explosion of research activity in this field has led to the
`identification of numerous naturally occurring endogenous peptides
`which act as neurotransmitters, neuromodulators, or trophic factors,
`to mediate nervous system functions. Increasing numbers of
`non-peptide ligands of neuropcptide receptors have been developed,
`which act as agonists or antagonists in pcptidergic systems.
`The journal provides a unique opportunity of integrating the many
`disciplines inrnlved in neuropeptide research. The journal publishes
`articles on all aspects of the neuropeptide field, with particular
`
`emphasis on gene regulation of peptide expression. peptide receptor
`subtypes, transgenic and knockout mice with mutations in
`genes for neuropeptides and peptides receptors, neuroanatomy,
`physiology, behaviour, neurotrophic factors. preclinical drug
`evaluation, clinicctl studies, and clinical trials.
`Original papers predominate. Manuscripts may be or any
`length, but must be complete studies; preliminary communications are
`not acccrted. Review articles and hypothesis papers arc welcomed. and
`will be evaluated in the same way as experimental papers. Authors
`intending to submit a review arc advised to communicate their inten(cid:173)
`tions to the Editor, to avoid possible duplication.
`www.neuropcp.com
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`

`

`Volume 38
`Numbers 2-3
`April/June 2004
`Pages 63-134
`
`www.neuropep.com
`
`This journal is indexed,
`abstracted and/or
`published online in the
`following media: Adonis,
`B/OS/S, Cambridge
`Scientific Abstracts,
`Chemical Abstracts,
`Current Awareness in Bio.
`Sciences, Current
`Contents/Life Sciences,
`Excerpta Medica/Embase,
`Index Medicus/Med/ine,
`Neuroscience Citation
`Index, Reference Update,
`Research Alert"', Science
`Citation Index, Scisearch"',
`UM/ (Microfilms), Academy
`of Sciences of Russia and
`BIOSIS Science Citation
`Index®.
`
`N europeptides
`
`Expression of the 11-opioid receptor In the anterior pituitary gland Is influenced by age and sex
`J. Carretero, P. Bodego, R.E. Rodriguez, M. Rubio, E. Blanco, and D.J. Burks
`Central pressor effects of CART peptides in anesthetized rats
`Ling-Ling Hwang, Chiung-Tong Chen, Tzu-Ling Li, Chiung-Zuan Chiu, and Shih-Fang Chi
`Change in the expression of NPY receptor subtypes Y1 and Y2 in central and peripheral
`neurons related to the control of blood pressure in rats following experimental
`hypertension
`E.F. Coelho, M.F.R. Ferrari, J.R. Maximino, and D.R. Fior-Chadi
`Evidence for the involvement of an opioid system in sciatic nerve of Rana rldibunda
`Y. Camlica, A. A!'i<in, and 0. c;:omelekoglu
`Ciliary neurotrophlc factor preferentially enhances spontaneous lgE production by B cells
`from atoplc patients
`H. Kimata
`Hyperglycemia Induced by acute central fluoxetlne administration: role of the central CRH
`system and 5-HT 3 receptors
`F. Carvalho, D. Barros, J. Silva, E. Rezende, M. Soares, J. Fregoneze, and E. De Castro e Silva
`Program
`
`Joint International Symposium on Calcitonin Gene-related Peptide, Amylln and
`Calcitonin 4th Symposium on Adrenomedullin and Proadrenomedullin N-20 Peptide, Zurich,
`Switzerland, March 18-20, 2004
`Walter Born and Jan A. Fischer
`Abstracts
`
`63
`
`69
`
`77
`
`83
`
`92
`
`98
`
`106
`
`Joint International Symposium on Calcltonln Gene-related Peptide, Amylln and
`Calcitonin; 4th Symposium on Adrenomedullin and Proadrenomedullin N-20 Peptide, Zurich,
`Switzerland, March 18-20, 2004
`
`110
`
`Conference report
`
`Highlights of the symposium: Prolonged survival in pulmonary hypertension and In myo(cid:173)
`cardial infarction with adrenomedullin, Improved glucose control In diabetes with amylin, and
`beneficial responses In acute migraine to a calcitonin gene-related peptide antagonist
`Jan A. Fischer and Walter Born
`Announcement
`
`132
`
`134
`
`Meetings Calendar
`
`Cover Image by Dr. Serguei Fetissov, Dr. Eugenia Kuteeva, and Professor Tomas Hokfelt, Department of Neuroscience, Karolinska Institute, Stockholm,
`Sweden.
`Cover shows an lmmunofluorescence confocal micrograph of the dorsal raphe nucleus (B7) of colchiclne-treated mouse double-labelled with rabbit antibodies to
`substance P (SP) (green) and guinea-pig antibodies to 5-hydroxytryptamine (5-HT) (red). A very dense SP fiber network Is surrounding the 5•HT cell bodies. The 5-
`HT cells are SP-negative. Note, however, at least four laterally located SP-positive cell bodies (green), which In the microscope have a faint red fluorescence, raising
`the possibility of a limited S·HT-SP coexistence. These cells are small and round. Note also the 5-HT fibers on top of the ependymal cell layer surrounding the
`aqueduct (top, middle). Magnification 360 X.
`The relationship between SP and 5-HT Is Interesting from many points of view, including the demonstration that an NK1 (SP) antagonist has as good an effect In
`major depression as a selective serotonin reuptake inhibitor (SSR1 ), but with a better side effect profile (Kramer et al., Science 281, 1640-1645, 1998). It has been
`assumed that in the rat, there is no SP - 5-HT coexistence in the (ascending) dorsal raphe 5-HT neurons, in contrast to the medullary (descending) 5-HT neurons,
`many of which can synthesize SP. However, it has been reported that also in rat a small percentage of dorsal raphe 5-HT neurons expresses substance P (Magoule
`et al., J. Histochem. Cytochem. 34, 735-742; Ma and Bleasdale, NeuroReport 13, 1809-1812, 2002). In the human many dorsal raphe neurons produce both
`messengers (Baker et al., Neuroscience 42, 757-775, 1991; Sergeyev et al., NeuroReport 10, 3967-3970, 1999), as they do in the monkey (Charara and Parent, J.
`Chem. Neuroanat. 15, 111-127, 1998), suggesting fn any case quantitative species differences. To what extent the 5-HT-SP coexistence in human is of any
`significance in depression and for the clinical efficacy of the NK1 antagonist, remains to be shown. We gratefully acknowledge supply of 5-HT antiserum by Dr. H.
`Steinbusch, Nijmegen and of SP antiserurm by Dr. L. Terenius, Stockholm.
`
`Also available on
`
`SCIENCE@DIRECT®
`
`www.sciencedirect.com
`
`

`

`Volume 38
`Numbers 2-3
`April/June 2004
`Pages 63-134
`
`www.neuropep.com
`
`This Journal is indexed,
`abstracted and/or
`published online in the
`following media: Adonis,
`8/0SIS, Csmbridge
`Scientific Abstracts,
`Chemical Abstracts,
`Current Awareness in Bio.
`Sciences, Current
`Contents/Life Sciences,
`Excerpts Medica/Embase,
`Index Medicus/Medllne,
`Neuroscience Citation
`Index, Reference Update,
`Research Ale~. Science
`Citation Index, Scisearch®,
`UM/ (Microfilms), Academy
`of Sciences of Russia and
`BIOSIS Science Citation
`Index®.
`
`~ilfli
`Neuropepfldes -· · · --·
`
`NLM 02775195 7
`
`e
`
`Expression of the µ-opioid receptor In the anterior pituitary gland Is Influenced by age
`and sex
`J. Carretero, P. Bodego, R.E. Rodriguez, M. Rubio, E. Blanco, and D.J. Burks
`
`Central pressor effects of CART peptides In anesthetized rats
`Ling-Ling Hwang, Chiung-Tong Chen, Tzu-Llng LI, Chiung-Zuan Chiu, and Shih-Fang Chi
`
`Change In the expression of NPV receptor subtypes V1 and V2 In central and peripheral
`neurons related to the control of blood pressure In rats following experimental
`hypertension
`E.F. Coelho, M.F.R. Ferrari, J.R. Maximina, and D.R. Flor•Chadi
`
`Evidence for the Involvement of an opioid system In sciatic nerve of Rana rldlbunda
`Y. r;:amllca, A. A~ln, and 0. r;:omelekoglu
`
`Clllary neurotrophlc factor preferentially enhances spontaneous lgE production by B
`cells from atoplc patients
`H. Klmata
`
`Hyperglycemia Induced by acute central fluoxetlne administration: role of the central
`CRH system and 5-HT 3 receptors
`F. Carvalho, D. Barros, J. Silva, E. Rezende, M. Soares, J. Fregoneze, and E. De Castro e Sliva
`
`Program
`Joint International Symposium on Calcltonln Gene-related Peptide, Amylln and
`Calcltonln 4th Symposium on Adrenomedullln and Proadrenomedullln N-20 Peptide,
`Zurich, Switzerland, March 18-20, 2004
`Walter Born and Jan A. Fischer
`
`Abstracts
`Joint International Symposium on Calcltonln Gene-related Peptide, Amylin and
`Calcltonln; 4th Symposium on Adrenomedullln and Proadrenomedullln N-20 Peptide,
`Zurich, Switzerland, March 18-20, 2004
`
`Conference report
`Hlghllghts of the symposium: Prolonged survival in pulmonary hypertension and In
`myocardial Infarction with adrenomedullln, Improved glucose control In diabetes with
`amylln, and beneficial responses In acute migraine to a calcitonln gene-related peptide
`antagonist
`Jan A. Fischer and Walter Born
`
`Announcement
`Meetings Calendar
`
`63
`
`69
`
`77
`
`83
`
`92
`
`98
`
`106
`
`110
`
`132
`
`134
`
`Also available on
`
`~c1eNcE@01RecT•
`
`www.sciencedirect.com
`
`.... .__
`
`

`

`Abstracts I Neuropeptides 38 (2004) J 10-131
`
`119
`
`significantly elevated food intake in obese Zucker rats
`while having no effect in lean controls.
`
`S24 Clinical use of amylin analogs
`D. Maggs, Amylin Pharmaceuticals Inc., San Diego,
`USA
`
`The pancreatic islets play a fundamental role in reg(cid:173)
`ulating fuel homoestasis and possibly body weight
`control. Historically, attention has focused on the role
`of the beta cell hormone insulin, that plays a role in
`assimilating fuel at times of feeding and restraining he(cid:173)
`patic glucose production when fasting; and glucagon,
`the alpha cell hormone, that opposes many of the ac(cid:173)
`tions of insulin by having counterregulatory actions to
`prevent hypoglycemia by sustaining or stimulating he(cid:173)
`patic glucose production when fasting. A third islet
`hormone amylin, secreted from the beta cells with in(cid:173)
`sulin, appears to have actions that complement those of
`insulin. While insulin stimulates glucose effiux, amylin
`regulates glucose influx by suppressing mealtime secre(cid:173)
`tion of glucagon, slowing gastric emptying and acting as
`a satiety signal. These findings are interesting when one
`considers that diabetes mellitus is a condition mani(cid:173)
`festing with degrees of beta cell failure and deficiencies
`of both insulin and amylin secretion. In the clinic this
`raises the question of whether some of the metabolic
`disturbance observed in the diabetic state could be at(cid:173)
`tributed to amylin deficiency and whether an interven(cid:173)
`tion to restore the amylin effect modifies the disease
`state. The amylin analog pramlintide has been devel(cid:173)
`oped to test this hypothesis.
`
`S25 Discovery and pharmacological profile of low
`molecular weight CGRP antagonists
`K. Rudolf, W. Eberlein, W. Engel, H. Doods, M.
`Entzeroth, G. Hallermayer, E. Bauer, Boehringer
`Ingelheim Pharma GmbH & Co. KG, 88397 Biberach
`an der Riss, Germany
`
`Calcitonin gene-related peptide (CGRP) is a 37 amino
`acid neuropeptide and one of the most potent endoge(cid:173)
`neous vasodilators known. Several lines of evidence
`suggest that CGRP plays a crucial role in the pathogen(cid:173)
`esis of migraine headache. CGRP antagonists may thus
`have therapeutic value for the treatment of migraine.
`Here, we report on the identification and pharmaco(cid:173)
`logical characterization of the first selective, low mo(cid:173)
`lecular weight CGRP antagonists. A screening effort led
`to the identification of BIBM 21, a dipeptide like com(cid:173)
`pound that showed weak but unequivocal inhibition of
`binding to the human CGRP receptor. Systematic
`structural variations of this initial screening hit led to
`potent CGRP antagonists,
`the prototype being
`BIBN4096.
`
`S26 CGRP antagonism as a new therapeutic principle in
`acute migraine
`J. Olesen '1, H.-C. Diener h,
`I.W. Husstedt c, P.J.
`Goadsby ", D. Hall C, U. Meier r, S. Pollentier r, L.M.
`Lesko C, BIBN4096BS Clinical Proof of Concept Study
`Group, a Department of Neurology, Glostrup Hospital,
`University of Copenhagen, Denmark, b Department of
`Neurology, University Essen, Germany, c Department
`of Neurology, University Hospital, Munster, Germany,
`d Institute of Neurology, Queen Square London, UK,
`e Boehringer Ingelheim Pharmaceuticals Inc., USA,
`r Boehringer Ingelheim Pharma KG, Germany
`
`Backgro1111d. Serotonin, 5-HTIB/ID receptor, agonists
`(triptans) are presently the only receptor specific drugs
`for migraine attacks. Calcitonin gene-related peptide
`(CGRP) may play a causative role in migraine. We
`therefore hypothesised that a CGRP antagonist might
`be effective in the treatment of migraine attacks.
`Methods. In an international, multi-center, double
`blind, randomised, clinical trial of BIBN4096BS, a
`highly specific and potent CGRP receptor antagonist, a
`total of 126 patients were treated with one of the fol(cid:173)
`lowing: placebo or BIBN4096BS 0.25; 0.50; 1.00; 2.50;
`5.00 or I 0.00 mg given intravenously over 10 min. A
`group sequential adaptive treatment assignment design
`was used to minimise the number of patients.
`Results. The 2.5 mg dose was selected and had a
`responder rate of 65.6'1/., versus 26.8% for placebo
`(P = 0.001). All active groups together had a responder
`rate of 60.0%. Significant superiority over placebo was
`also observed for most secondary parameters: pain free
`at 2 h, sustained response over 24 h, headache recur(cid:173)
`rence, nausea, photophobia, phonophobia, improve(cid:173)
`ment in functional capacity and time to meaningful
`relief. An effect was apparent after 30 min and in(cid:173)
`creased over the next few hours. The overall adverse
`event rate was 25% after 2.5 mg and 20% for all active
`doses versus 12.2% for placebo. The most frequent side
`effect was paraesthesias. There were no serious adverse
`events.
`Co11cl11sio11s. BIBN4096BS is effective in the acute
`treatment of migraine and the present study, therefore,
`establishes a totally novel principle in the acute treat(cid:173)
`ment of migraine: CGRP antagonism.
`
`S27 Targeted regulation of CGRP gene expression
`A.F. Russo", T.J. Viney", T.W. Schmidt", P.X.
`Dong", Z. Zheng", C. Firm", J.M. Dickerson h, P.L.
`Durham C, " Department of Physiology and Biophysics,
`University of Iowa, Iowa City, IA 52242, USA,
`b Department
`of Neurobiology, University
`of
`Rochester, Rochester, NY, USA,
`c Department. of
`Biology,
`Southwest Missouri
`State University,
`Springfield, MO 65804, USA
`
`