Volume 448
`
`NEURONAL CHOLECYSTOKININ
`
`Edited by Jean-Jacques Vanderhaeghen and Jacqueline N. Crawley
`
`The New York Academy of Sciences:
`New York, New York
`1985
`
`
`
`
`MAIA Exhibit 1008
`MAIA V. BRACCO
`IPR PETITION
`
`

`

`;'' ·t
`
`Copyright o 1985 by TM New York Academy of Sciences. All rights reserved. Under the provisions of the
`United States Copyright Act of 1976, individual readers of the Annals qre permilled to make fair use of the
`material in them for teaching or research. Permission is granted to quote from the Annals provided that the
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`permission of The Academy. Address Inquiries to the Executive Editor at The New York Academy of
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`
`Copying fees: For each copy of an article made beyond the free copying perm/lied under Section /07 ·or /08
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`Salem, MA 01970. For articles more than 3 pages, the copying fee Is $1.75.
`
`Cover: Autoradiographic localization of cho/ecystoklnin receptors in rat forebraln by Pierrette Gaudreau,
`Notre Dame Hospital, Montreal. Canada. (Paperback volume only.)
`Library of Congress Cataloging in Publication Data
`
`Main entry under title:
`
`Neuronal cholecystokinin.
`(Annals of the New York Academy of Sciences, ISSN 077-8923; v. 448)
`Based on the First International Conference on Neuronal Cholecystokinin, held in Brussels,
`Belgium, July 3- 6, 1984, sponsored by the Queen Elisabeth Medical Foundation of Belgium and
`lhe New York Academy of Sciences.
`Includes bibliographies and indexes.
`1. Cholecystokinin--Physiological effect- Congresses.
`2. Neurons-Congresses. 3. Central nervous system-Congresses.
`Jacques.
`III. International Conference
`11. Crawley, Jacqueline N.
`on Neuronal Cholecystokinin (Isl : 1984 : Brussels,
`IV. Fondation Medicale Reine Elisabeth.
`Belgium)
`V. New York Academy of Sciences. VI. Series.
`[DNLM : I. Cholecystokinin-congresses. 2. Neurons(cid:173)
`congresses. WI AN626YI v. 448/WK 170 N494 1984)
`85- 13756
`599'.0188
`QP572.C5N48 1985
`ISBN 0-89766-290-3
`ISBN 0-89766-291-1 (pbk.)
`
`I. Vanderhaeghen, Jean(cid:173)
`
`i
`1··
`j! .,
`
`SP
`Printed in the United States of America
`ISBN 0-89766'-290-3 ( cloth)
`ISBN 0-89766'-291-l (paper)
`ISSN 077-8923
`
`
`
`
`

`

`6 tt)ll'AeJ
`'Wt
`ANNALS OF THl:!lNI~v YORK ACADEMY OF SCIENCES N <::. ½.(
`\J, ~-'{·cv
`
`.
`
`; Volume 448
`July 5, 1985
`NEURONAL ·cHOLECYSTOKININ°
`
`ions of the
`use of the
`,d that the
`d only by
`,ademy of
`
`,07 or 108
`ess Street.
`
`Jaudreau,
`
`Brussels,
`:iumand
`
`:n, Jean-
`
`Editors and Conference Organizers
`JEAN-JACQUES VANDERHAEGHEN AND JACQUELINE N. CRAWLEY
`
`CONTENTS
`
`Preface. By JEAN-JACQUES V ANDERHAEGHEN AND JACQUELINE N. CRAWLEY...
`Comparative Distribution of Cholecystokinin and Other Neuropeptides: Why is
`This Peptide Different from AH Other Peptides? By JACQUELINE N.
`CRAWLEY········································································································
`Part I. Neurochemistry
`Molecular Forms ofCholecystokinin in the Nervous System. By MICHAEL J.
`BROWNSTEIN and JENS F. REHFELD...............................................................
`Molecular Forms of Cholecystokinin.in the Brain and the Relationship to
`Neuronal Gastrins. By J. F. REHFELD, H.F. HANSEN, P. D. MARLEY, and
`K . STENGAARD-PEDERSEN ··············································································
`Studies on Brain Cholecystokinin in Different Species Using Sequence-specific
`Antisera. By J.B. M. J. JANSEN and C. B. H. W. LAMERS...........................
`Cholecystokinin and Gastrin Forms in the Nervous System. By G. J. DOCKRAY,
`H. DESMOND, R. J. GAYTON, A-C. JONSSON, H. RAYBOULD, K. A.
`SHARKEY, A. VARRO, and R. G. WILLIAMS...................................................
`Neurochemistry of Cholecystokinin in Brain, Pituitary, and Cerebrospinal
`Fluid. By MARGERY C. BEINFELD and ANITA CIARLEGLIO...........................
`
`xiii
`
`9
`
`11
`
`24
`
`32
`
`44
`
`Part II. Synthesis and Metabolism
`Modulation ofCholecystokinin Gene Expression. By ROBERT J. DESCHENES,
`RANDY s. HAUN, DAN SUNKEL, BERNARD A. Roos, and JACK E. DIXON...
`Studies on the Conformation, Enzymatic Degradation, Pharmacological
`Potency, and Binding Properties in Brain Tissue of Cholecystokinin-8 and
`New ~elated Peptides. By B. P. ROQUES, C. DURIEUX, G. GACEL, D.
`FELAPRAT, M. RUIZ-GAYO, J. BELLENEY, E. FELLION, J.M. ZAJAC, M-C.
`FOURNIE-ZALUSKI, V. DAUGE, I. MENANT, P. ROSSIGNOL, B. Lux, D.
`GERARD, D. BEGUE, A. SASAKI, and J. L. MoRGAT ......................................
`The Biosynthesis of Cholecystokinin in Neural Tissue. By NILS R.
`GOLTERMANN ············································································:....................
`76
`aThis volume is the result of a conference on Neuronal Cholecystokinin held by The New York
`Academy of Sciences and the Fondation Medicale Reine Elisabeth on July 3-6, 1984 in Brussels,
`Belgium.
`
`61
`
`53
`
`
`
`
`

`

`87
`99
`
`Enzymatic Degradation of Cholecystokinin in the Central Nervous System. By
`MONIQUE DEScH9.DT-\tNCKMAN. .......................... .......................................
`Cholecystokinin in Intracerebral Transplants. By M. SCHULTZBERG ..... ..............
`Sulfation and Desulfation of Cerebral Cholecystokinin. By FROYLAN VARGAS,
`OLIVIER FREROT, MI DAM TRUNG TUONG, KATHERINE ZUZEL,
`CHRISTIANE ROSE, and JEAN-CHARLES SCHWARTZ ...................................... 110
`Part III. Neuroanatomy
`The Distribution and Some Connections of Cholecystokinin Neurons in the Rat
`Brain. By JAMES H. FALLON and KIM B. SEROOGY ........... .. ......................... 121
`Studies on Cholecystokinin-containing Neuronal Pathways in Rat Cerebral
`Cortex: and Stria tum. By D. K. MEYER and Z. PROTOPAPAS ........................ 133
`Anatomical Studies of Cholecystokinin in Neurons and Pathways Involved in
`Neuroendocrine Regulation. By JOZSEF Z . KISS ... ........................................ 144
`Cholecystokinin in the Medial Parvocellular Subdivision of the Paraventricular
`Nucleus: Co-existence with Corticotropin-releasing Hormone. By E .
`. MEZEY, T. D. REISINE, L. SKIRBOLL, M. SEINFELD, and J. z. KISS. .. ......... . 152
`Cholecystokinin in the Retina of Vertebrates. By NEVILLE N. OSBORNE ........ :.... 157
`Cholecystokinin in the Nervous Systems of Invertebrates and Protochordates:
`Immunohistochemical Localization of a Cholecystokinin-8-like Substance
`in Annelids and Insects. By N. DHAINAUT-COURTOIS, G. TRAMU, R.
`MARCEL, J. MALECHA, M. VERGER-BOCQUET, J.C. ANDRIES, M.
`MASSON, L. SELLOUM, G. BELEMTOUGRI, and J . C. BEAUVILLAIN ............... 167
`Part IV. Receptors
`Integrated Anatomical and Physiological Studies of Neuronal Cholecystokinin
`Receptors. By ROBERT B. INNIS and GEORGE K. AGHAJANIAN .................. .. 188
`Cholecystokinin Receptors in Mammalian Brain: A Comparative
`Characterization and Visualization. By PIERRETTE GAUDREAU, SERGE
`ST-PIERRE, CANDACE B. PERT, and REM! QUIRION........ .............................. 198
`Brain Cholecystokinin Receptors: Binding Characteristics, Covalent
`Cross-linking, and Evolutionary Aspects. By JOHN A. WILLIAMS, STEVEN
`R. VIGNA, CHOITSU SAKAMOTO, and IRA D. GOLDFINE ................................ 220
`Cholecystokinin Neuron Systems and Their Interactions with the Presynaptic
`Features of the Dopamine Neuron Systems: A Morphometric and
`Neurochemical Analysis Involving Studies on the Action of
`Cholecystokinin-8 and Cholecystokinin-58. By K. FuxE, L. F. AGNATI,
`J-J. VANDERHAEGHEN, K. TATEMOTO, K. ANDERSSON, P. ENEROTH, A.
`HARFSTRAND, G. VON EULER, R. TONI, M. GOLDSTEIN, and V. Murr ....... 231
`Part V. Co-existence
`Distribution of Cholecystokinin-like Immunoreactivity in the Nervous System:
`Co-existence with Classical Neurotransmitters and Other Neuropeptides.
`By T. H6KFELT, L. SKIRBOLL, 8. EVERITT, 8. MEISTER, M. BROWNSTEIN,
`T . JACOBS, A. FADEN, S. KUGA, M. GOLDSTEIN, R. MARKSTEIN, G.
`DOCKRAY, and J. REHFELD ......................................... ····:· .. ···........................ 255
`Electrophysiological Studies of the Role of Cholecystokinin in the Substantia
`Nigra and Its Interactions with Dopamine. By L. R. SKIRBOLL and D. W.
`HOMMER ......... ............... ................................ ........................... .................... .. 275
`
`
`
`
`

`

`iystem. By
`
`-1 VARGAS,
`
`, in the Rat
`
`:erebral
`
`volved in
`
`87
`99
`
`110
`
`121
`
`133
`
`144
`
`152
`157
`
`ventricular
`1yE.
`:1ss ............ .
`lNE ........... . .
`:hordates:
`Substance
`u,R.
`vi.
`IN .. ............. 167
`
`:cystokinin
`................... 188
`
`SERGE
`................... 198
`
`S,STEVEN
`................... 220
`·esynaptic
`nd
`
`~GNATI,
`'.OTH,A.
`MUTT ....... 231
`
`JS System:
`opeptides.
`>WNSTEIN,
`1,G.
`.................. 255
`1bstantia
`mdD.W.
`.................. 275
`
`Cholecystokinin Potentiation of Dopamine-mediated Behaviors in the Nucleus
`Accumbens. By JACQUELINE N . CRAWLEY ................................. : ................ ..
`In Vivo Sulfatio~7o'f"ct'btecystokinin Octa peptide: Possible Interactions of the
`Two Forms of Cholecystokinin with Dopamine in the Brain. By B. PENKE,
`G. L. KovAcs, J. ZSIG6, T. KADAR, G. SZABO, K. KovAcs, and G.
`TELEGDY ................................................... .................................................... ..
`Distinct Properties of Cµolecystokinin-8 and Mixed Dopamine(cid:173)
`Cholecystokinin-8 Neurons Innervating the Nucleus Accumbens. By J.M.
`STUDLER, M. REIBAUD, G. TRAMU, G. BLANC, J. GLOWINSKI, and J.P.
`TASSIN ................................. .......... .................. : .............................................. .
`Evidence for Cholecystokinin-Dopamine Receptor Interactions in the Central
`Nervous System of the Adult and Old Rat: Studies on Their Functional
`Meaning. By L. F. AGNATI, K. FuxE, L. GIARDINO, L_,.CALZA, M. Zou,
`N. BATTISTINI, F. BENFENATI, J-J. VANDERHAEGHEN, D. GUIDOLIN, M .
`RUGGERI, and M. GOLDSTEIN ....................................................................... .
`Co-existence of Cholecystokinin- or Gastrin-like Peptides with Other Peptides
`in the Hypophysis and the Hypothalamus. By J-J. VANDERHAEGHEN, S.
`GOLDMAN, F. LOTSTRA, 0. VAN REETH, C. DESCHEPPER, J. ROSSIER, and
`S. SCHIFFMANN .............. ...... ................... .............................. .......................... .
`
`283
`
`293
`
`306
`
`315
`
`334
`
`Part VI. Neurophysiology
`Further Studies on the Specificity of Proglumide as a Selective Cholecystokinin
`Antagonist in the Central Nervous System. By B. S. BUNNEY, L.A.
`CHIODO, and A. s. FREEMAN ........... ,.. ........................................................... 345
`Interactions of Cholecystokinin and Dopamine in the Nucleus Accumbens. By
`REX Y. WANG, FRANCIS J . WHITE, and MARK M. VOIGT .................. ;......... 352
`Cholecystokinin as a Potent Excitant of Neurons of the Dentate Gyms of Rats.
`By PENNY A. BROOKS and JOHN s. KELLY.. .............. ..................................... 361
`The Effects of Cholecystokinin-8 in the Nucleus Tractus Solitarius. By
`M. DENAVIT-SAUBIE, M. A. HURLE, M. P. MORIN-SURUN, A. S. FOUTZ,
`and J. CHAMPAGNAT ........................................................................ · .... '........... 375
`Actions of Cholecystokinin Octapeptide on Rat Spinal Dorsal Horn Neurons.
`By J. WILLETTS, L. URBAN, K. MURASE, and M. RANDIC ................. :.......... 385
`Cholecystokinin and Cultured Spinal Neurons: Immunohistochemistry,
`Receptor Binding, and Neurophysiology. By M.A. ROGAWSKI, M. C.
`SEINFELD, s. E. HAYS, T. HOKFELT, and L. R. SKIRBOLL ............................ 403
`
`Part VII. Behavio~ ·
`Species Differences in the Response to Cholecystokinin. By JOHN E. MORLEY,
`ALLENS . LEVINE, TIMOTHY J. HARTNESS, STEVEN E. NIZIELSKI, MICHAEL
`J. SHAW, and J<,>HN J. HUGHES.......... .. .......................... ............ .................... 413
`The Satiety Effect of Cholecystokinin: Recent Progress and Current Problems.
`By G. P. SMITH and J. GIBBS..... ..................................................................... 417
`Central Nervous System Cholecystokinin and the Control of Feeding. By
`CLIFTON A. BAILE and MARY ANNE DELLA-FERA ~ ................................... ,.. 424
`Satiety Effects of Cholecystokinin and Ceruletide in Lean and Obese Man. By
`GEORG STACHER .. ...................... .. ..................................... .............................. 431
`
`-
`
`. - -- ----
`
`
`
`
`

`

`Opiate Antagonistic Function of Cholecystokinin in Analgesia and Energy
`Balance Systems. By PATRICIA L. FARIS....................................................... 437
`Neuropharmacological Profile._ofc~fecystokinin-like Peptides. By GERHARD
`ZETLER ....................................... : ...................................... ·.............................. 448
`Psychopharmacological Profile of Cholecystokinin Using the Self-Stimulation
`and the Drug Discrimination Paradigms. By P. DE WITTE, E. SWANET,
`M. GEWISS, s. GOLDMAN, B. ROQUES, and J-J. YANDERHAEGHEN .............. 470
`Part VIII. Clinical Significance
`Cholecystokinin Content in the Basal Ganglia in Huntington's Disease: The
`Expression of Cholecystokinin Immunoreactivity in Stria ta! Grafts to
`lbotenic Acid-lesioned Rat Striatum. By P. C. EMSON, D. DAWBARN,
`M. N. RossoR, J. F. REHFELD, P. BRUNDIN, 0. ISACSON, and A.
`BJORKLUND·························································································;··········· . 488
`Reduced Cholecystokinin Levels in the Limbic Lobe in Schizophrenia: A
`Marker for Pathology Underlying the Defect State? By I. N. FERRIER,
`T. J. CROW, s. M. FARMERY, G. w. ROBERTS, F. OWEN, T. E. ADRIAN,
`and S. R. BLOOM............................................................................................ 495
`Reduced Cholecystokinin Levels in Cerebrospinal Fluid of Parkinsonian and
`Schizophrenic Patients: Effect of Ceruletide in Schizophrenia. By
`F. LOTSTRA, P. M. P. YERBANCK, C. GILLES, J. MENDLEWICZ, and
`J-J. VANDERHAEGHEN .................................................................................... 507
`Antipsychotic Effects of Ceruletide in Chronic Schizophrenia: An Appraisal of
`the Long-term, Intermittent Medication of Ceruletide in Chronic
`Schizophrenia. By T AKASHI MOROJI, Kmcm ITOH, and Kozo ITOH ........... 518
`Clinical and Neuroendocrine Studies with Cholecystokinin Peptides. By
`N. P. V. NAIR, D. BLOOM, S. LAL, G. DEBONNEL, G. SCHWARTZ, and S.
`MOSTICYAN ···································································································· 535
`The Effects of Cholecystokinin-like Peptides in Schizophrenics and
`Normal Human Subjects. By DANIEL W. HOMMER, DAVID PICKAR,
`JACQUELINE N. CRAWLEY, HERBERT WEINGARTNER, and STEVEN M.
`PAUL................................ ... ................................... .......................................... 542
`Cholecystoki nin-mediated Synaptic Function and the Treatment of
`Neu.ropsychiatric Disease. By T. N. CHASE, P. BARONE, G. BRUNO, S. L.
`COHEN, j_ JUNCOS, M . KNIGHT, s. RUGGERI, L. STEARDO, and C. A.
`TAMMINGA.................................................................................... .................. 553
`Poster Papers
`Distribution of Cholecystokinin-like Immunoreactivity in the Brainstem
`Auditory System. By J.C. ADAMS and E. MUGNAINI................................... 563
`A New Specific Assay for Cholecystokinin Octapeptide. By T. E. ADRIAN,
`A. J. BACARESE-HAMILTON, ands. R. BLOOM.............................................. 566
`Cholecystokinin-like Immunoreactivity in the Rat Nucleus Accumbens: An
`Ultrastructural Study. By H. BAALI-CHERIF, M. ARLUISON, and G. TRAMU
`Prevention of Cholecystokinin Oxidation During Tissue Extraction: A Major
`Problem Solved. By A. J. BACARESE-HAMILTON, T. E. ADRIAN, and S. R.
`BLOOM .. · .............................................. ................... ......................... :................ 571
`Antagonism of Cholecystokinin by Naloxone and Proglumide in Mice. By B. S.
`BARBAZ, w. L. AUTRY, F. G. AMBROSE, R. GERBER, and J.M. LIEBMAN... 573
`
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`.. 542
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`
`Antagonism of Cholecystokinin-induced Activation by Benzodiazepine
`Receptor Agonists: Mtcroi11Jtophoretic Studies in the Rat Hippocampus.
`By JACQUES BRADWEfN an~ CLAUDE DEMONTIGNY .................................... 575
`Lack of Competition between Two Reputed Peripheral Cholecystokinin
`Receptor Antagonists for Central Cholecystokinin Binding Sites. By
`COLIN R. CLARK, PETER DAUM, and JOHN HUGHES..................................... 581
`Cholecystokinin-like Immunorea~tivity in the Dorsal Horn of the Rat Spinal
`Cord. By M. CONRATH-VERRIER, M. DIETL, and G. TRAMU........................ 583
`Tracing the Sensory Pathway from the Gut to Brain Regions Mediating the
`Actions of Cholecystokinin on Feeding and Exploration. By JACQUELINE
`N. CRAWLEY and JOZSEF z. Kiss.................................................................. 586
`Distribution ofCholecystokinin-containing Neurons in Cat Visual Cortex. By
`H. DEMEULEMEESTER, F. VANDESANDE, and G. A. ORBAN .......................... 589
`Degradation Processes and Binding Properties of Cholecystokinin and Related
`Compounds: Studies Using a New Tritiated Ligand. By CHRISTIANE
`DURIEUX, DIDIER PELAPRAT, JEAN MARIE ZAJAC, MARIE-CLAUDE
`FOURNIE-ZALUSKI, GILLES GACEL, and BERNARD P. ROQUES ...................... 593
`Forebrain Projections from Midbr~in Cholecystokinin-containi~g Neurons in
`the Rat. By JAMES H. FALLON and KIM B. SEROOGY ................................... 596
`Conformational Analysis and Structural Activity Relationships of
`Cholecystokinin Peptides. By M-C. FoURNIE-ZALUSKI, J. BELLENEY,
`C. DuR1Eux, G. GACEL, B. P. ROQUES, D. BEGUE, I. MENANT, B. Lux,
`and D. GERARD.......... ..................................................................................... 598
`Changes in Cholecystokinin Content in Rat Brain after Subchronic Treatment
`with Neuroleptics. By PETER FREY................................................................ 601
`Central versus Peripheral Cholecystokinin Octapeptide on Self-Stimulation and
`Locomotor Activity in the Rat. By A. J. GOWER and C. L. E. BROEKKAMP. 604
`Depolarization-evoked Release of Endogenous Dopamine and Cholecystokinin
`from Rat Striatal Slices. By J.B. HUTCHISON, S. R. NAHORSKI, and
`J. STRUPISH . .-............................. :..................................................................... 607
`Effects on Ascending Nociceptive Activity in the Rat Spinal C9rd Produced by
`Cholecystokinin Octapeptide, Ceruletide, and Morphine Injected into the
`Periaqueductal Gray Matter. By ILMAR JURNA and GERHARD ZETLER ...... 609
`Molecular Cloning of the Human Cholecystokinin Gene. By KIKUYA KATO,
`YOOSUKE TAKAHASHI, and KENICHI MATSUBARA........................................ 613
`Behavioral Effects of Cholecystokinin and Vasoactive Intestinal Peptide in
`Neofrontal-decorticated Rats. By GORO KATSUURA and SHINJI ITOH ......... 616
`The Pyloric Cholecystokinin Receptor: A Site of Mediation for Satiety? By
`TIMOTHY H. MORAN, PAUL H. ROBINSON, and PAUL R. MCHUGH............. 621
`Autoradiographic Localization of Cholecystokinin Receptors in Human Brain.
`By REMI QUIRION, CATHERINE CSONKA, PIERRE ETIENNE, N. P. V. NAIR,
`YVES ROBITAILLE, and PIERRETTE GAUDREAU.............................................. 624
`Gastric Cholecystokinin Receptors and the Effect of Cholecystokfnin on
`Feeding and Gastric Emptying in the Neonatal Rat. By PAUL H.
`ROBINSON, TIMOTHY H. MORAN, and PAUL R. MCHUGH...................... ...... 627
`
`
`
`
`

`

`Effects of Proglumide on Morphine Analgesia and Tolerance. By LUCIO C.
`ROVATI, PAOLA SACE~P0T.il and ALBERTO E. PANERAI .............................. .
`The Effects of Cholecystqltinin ~ctapeptide and Proglumide on Electrically
`Elicited Eating. By LINDA H. SCHNEIDER, JOEL M. KAPLAN, SAMUEL M.
`FELDMAN, EDGAR E. COONS, and RANDALL B. MURPHY ............................ .
`Cholecystokinin Innervation of Rat Cerebral Cortex. By KIM B. SEROOGY and
`JAMES H. FALLON .......................................................................................... .
`Cholecystokinin Octapeptide Action on Gastric Emptying and Food Intake in
`Normal and Vagotomized Man. By M. J. SHAW, J. J. HUGHES, J.E.
`MORLEY, A. s. LEVINE, s. E. SILVIS, and R. B. SHAFER ....................... ...... ..
`Naloxone Potentiation of the Antinociceptive Action of Caerulein. By M. J.
`SHEEHAN and J. DE BELLEROCHE ................................................................. ..
`Increased Food Intake in the Rat Caused by Proglumide, the Cholecystokinin
`Antagonist: An Effect Abolished by Vagotomy. By G. SHILLABEER and
`J. s. DAVISON ................................................................................................ .
`Cholecystokinin in Discrete Rat Brain Regions as a Function of Sex and
`Estrous Cycle. By R. A. SIEGEL, M. FRANKFURT, U. PAHNKE, and
`W. WUTIKE .......................... : ........................................................................ .
`The Effect of Cholecystokinin on a Behavioral Satiety Deficit in Obese Mice.
`By ALAN J. STROHMAYER ............................................................................ ..
`Cholecystokinin Octapeptide Inimunoreactivity Distribution in Human Brain:
`Modifications in Parkinsonian Patients. By J.M. STUDLER and
`F. JAVOY-AGID ............................................................................................. ..
`The Potentiation of Morphine-induced Inhibition of Spinal Transmission by
`Proglumide, a Putative Cholecystokinin Antagonist. By S. N. SUBERG,
`E. s. CULHANE, E. CARSTENS, and L. R. w ATKINS .................................... ..
`Cholecystokinin Octapeptide's Effect on Local Cerebral Glucose Utilization in
`the Laboratory Rat. By C. A. TAMMINGA, G. LUCIGNANI, L. J. PORRINO,
`and T. N. CHASE ........................................................................................... .
`Metabolism of Cholecystokinin by Endopeptidase-24.11. By ANTHONY J.
`TURNER, REBECCA MATSAS, and A. JOHN KENNY ...................................... .
`Accumbens Cholecystokinin Attenuation of Brain Stimulation Reward in the
`Ventral Tegmental Area. By F. J. VACCARINO and G. F. Koos .................. .
`Neuroleptic-like Activity and Antipsychotic Action of Cholecystokinin-related
`Peptides. By JAN M. VAN REE and DAVID DE WIED ..................................... .
`Effects of Cholecystokinin on Dopamine Release in the Nucleus Accumbens.
`By MARK M. VOIGT, REX Y. WANG, and THOMAS C. WESTFALL .............. ..
`The Enhancement of Opiate Analgesia and the Possible Reversal of Morphine
`Tolerance by Proglumide. By L. R. WATKINS, I. B. KINSCHECK,
`G. ROSENQUIST, J. MILLER, S. WIMBERG, H. FRENK, E. KAUFMAN,
`R. COGHILL, S. N. SUBERG, and D. J. MAYER ............................................. .
`Characterization of Cholecystokinin Recognition Sites in Mouse Cerebral
`Cortex Using a Radiolabeled Octapeptide. By LAWRENCE WENNOGLE,
`DOUGLAS STEEL, and BARBARA PETRACK ............................... = ...................... .
`Effects of Chronic Treatment with Cholecystokinin on Mid brain Dopamine
`Neurons. By FRANCIS J. WHITE and REX Y. WANG ................................... ..
`
`630
`
`633
`
`636
`
`640
`
`642
`
`648
`
`651
`
`654
`
`656
`
`660
`
`663
`
`666
`
`669
`
`671
`
`674
`
`676
`
`678
`
`682
`
`JI
`
`;
`I
`'t
`'!
`I
`I
`lr
`i
`~
`F
`G
`L
`L
`L
`L•
`
`M
`M
`M
`
`N.
`N,
`A,I
`R(j
`SAi
`sa,
`(
`SH
`STt
`E.~
`Uf\
`U1'
`TH
`VA
`W)
`
`
`
`
`

`

`630
`
`633
`
`636
`
`640
`
`642
`
`648
`
`·651
`
`654
`
`656
`
`660
`
`663
`
`666
`
`669
`
`671
`
`674
`
`y
`.M.
`
`and
`
`:in
`
`r.
`
`nin
`d
`
`;e.
`
`ain:
`
`y
`
`nin
`NO,
`
`he
`
`1ted
`
`IS.
`
`.ine
`
`........ 676
`
`678
`
`682
`
`Assessment of the Role of "Enkephalinase" in Cholecystokinin Inactivation. By
`KATHERINE A. 2¥ZE~CHRISTIANE ROSE, and JEAN-CHARLES SCHWARTZ 685
`,
`''
`Index of Contributors ........ \'.................................................................................... 687
`Subject Index ................. ,............ .......................... ................................................. 691
`Financial assistance was received from:
`ABBOTT LABORATORIES
`ANALIS S.A., LABORATORY INSTRUMENTS
`CIBA-GEIGY CORPORATION/PHARMACEUTICALS'DIVISION
`E.I. DU PONT DE NEMOURS & COMPANY /CENTRAL RESEARCH AND
`DEVELOPMENT DEPARTMENT/PHARMACEUTICALS, BIOMEDICAL
`PRODUCTS DEPARTMENT
`FARMITALIA CARLO ERBA, S.A.
`FIDIA RESEARCH LABORATORIES
`FONDA TION MEDI CALE REINE ELISABETH
`FONDS NATIONAL DE LA RECHERCHE SCIENTIFIQUE BELGE
`GROUPE DE RECHERCHE SERVIER
`LABORATOIRE FOURNIER
`LABO RA TOIRE RHONE-POLENC SANTE
`LABO RA TOIRE ROUSSEL UCLAF
`LOTERIE NATIONALE BELGE
`MERCK SHARP & DOHME RESEARCH LABORATORIES
`MICRO BELGIUM APPLICATION
`MILLIPORE, S.A./WATERS PRODUCT DIVISION-BELGIUM
`MINISTERE DE L'EDUCATION NATIONALE ET DE LA CULTURE FRAN(;AISE
`BELGE
`NATIONAL INSTITUTE OF MENTAL HEALTH-NIH, USA
`NATIONAL SCIENCE FOUNDATION, USA
`A.H. ROBINS COMPANY /RESEARCH AND DEVELOPMENT DIVISION
`ROCHE-BELGIQUE
`SANDOZ, LTD.
`SEARLE RESEARCH AND DEVELOPMENT /DIVISION OF G.D. SEARLE &
`COMPANY
`SH.IONOGI RESEARCH LABORATORIES/SHIONOGI & COMPANY, LTD.
`STUART PHARMACEUTICALS/DIVISION OF ICI AMERICAS, INC.
`E.R. SQUIBB & SONS, INC.
`UNION CHIMIQUE BELGE/BIOPRODUCTS
`UNITED STATES AIR FORCE OFFICE OF .SCIENTIFIC RESEARCH
`THE UPJOHN COMPANY-BELGIUM
`VAN HOPPL YNUS OPTIQUE
`WARNER LAMBERT COMPANY /PHARMACEUTICAL RESEARCH DIVISION
`
`The New York Academy of Sciences believes that it has a responsibility to provide an open
`foru m for discussion of scientific questions. The positions takel) by the authors of the
`papers that make up this A1111al are their own and not necessarily those of the Academy.
`The Academy has no intent to influence legislation by providing such forums.
`
`
`
`
`

`

`Preface
`
`,,h• ,r "t-
`The discovery of cholfcyst~inin in vertebrate brain spawned a growing interest in ,
`the role of this peptide in central neural function. The wide distribulion of cholecysto(cid:173)
`kinin in the nervous system, and its co-existence with classical neutrotransmitters and
`other neuropeptidcs, suggest that cholecystokinin may open new avenues in our
`understanding and treatment of several neuropsychiatric disorders, including schizo(cid:173)
`phrenia and depression.
`The First International Conference on Neuronal Cholecystokinin was held in
`Brussels, Belgium, July 3-6, 1984. Sponsored by the· Queen Elisabeth Medical
`Foundation of Belgium and the New York Academy of Sciences, the conference
`gathered 200 participants. Scientific sessions included 47 symposium and 44 poster
`presentations, most of which are included in this volume. We wish to express our deep
`appreciation to the chairmen, speakers, and poster authors. The high level of their
`scientific contributions to the meeting has made this book possible.
`We extend our heartfelt appreciation to the many dedicated and generous people
`involved in the organization of this conference, as well as to those involved in the
`publication of this volume. Professor Pierre Paul Lambert, Director of the Queen
`Elisabeth Medical Foundation, provided the initial resources for locating the meeting
`in Brussels, in the majestic Palais des Academies. Dr. Dennis Kelly of the Conference
`Committee of the New York Academy of Sciences and Mrs. Ellen Marks, Mrs. Renee
`Wilkerson, and Mr. Phillip Allen of the Academy's Conference Department coordi(cid:173)
`nated numerous aspects of the conference; Mr. Kevin M. Mayer of the Editorial
`Department provided a careful editing of this volume.
`We are grateful to the Belgian Fonds National de la Recherche Scientifique and to
`tJ1e Belgian Ministere de !'Education Nationale et de la Culture Fran9aise for their
`financial support. The many generous financial contributions from pharmaceutical
`companies are tha nkfully acknowledged. Our friends Professor Kjell Fuxe in Sweden;
`Professor Bernard Roques in France; and Guy Pire, Willy Stekke, and Fran9ois
`Xhonneux in Belgium have helped us greatly to find additional financial support for
`the meeting. The benevolent help of Roger a.nd Addy Eggericks, Serge Goldmann,
`Marise Gombert, and Pierre Vanderhaeghen was greatly appreciated in various
`aspects of the organization of the conference.
`We were deeply honored by Her Majesty the Queen Fabiola of Belgium for her
`attendance at the conference. Her presence during a morning session and her informal
`discussion with several participants in a reception after that ession have shown us her
`interest in the ncurosciences. Her intellectual support is a great stimulant for our work,
`and therefore we are happy to respectfully dedicate this volume to Her Majesty the
`Queen Fabiola of Belgium.
`
`JEAN-JACQUES V ANDERHAEGHEN
`JACQUELINE N. CRAWLEY
`
`xiii
`
`
`
`
`

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`

`

`Prevention of Cholecystokinin Oxidation
`During yissue Extraction
`A Major Problem Solved
`
`1'·
`
`'
`
`. Natl.
`
`9-257.
`. 1980 .
`
`. d.Sci.
`
`. USA
`
`STl!IN,
`
`A. J. BACARESE-HAMILTON, T. E. ADRIAN,
`AND S. R. BLOOM
`Royal Postgraduate Medical School
`Hammersmith Hospital
`London WI 2 OHS, England
`
`Cholecystokinin (CCK) is particularly susceptible to oxidation of its methionine
`residues (of which CCK-33 has three, and CCK-8 two) which can cause loss both of
`immunoreactivity and of biological potency. The degree of oxidation of solutions of
`pure CCK standards and of endogenous CCK porcine peptides was investigated using
`high resolution, reverse-phase HPLC with radioimmunoassay as the detection
`system.
`Reverse-phase HPLC was performed on a 5 µ. Techsil C-18 column (HPLC
`Technology, Ltd.) eluted isocratically with 30% CH 3CN/water with 0.05% trifluoro(cid:173)
`acetic acid at a flow rate of I ml/min. The column was subsequently eluted with 50%
`CH3CN/water :rncl re-equilibrated with 30% CH3CN/water. Prior to loading, all
`tissue extracts and standards were prepared on aµ. Bondapak C-18 cartridge (Waters)
`eluted with 50% CH3CN /water with 0.05% trifluoroacetic acid. After centrifugation
`
`TABLE t. Effect of Oxidation and Reduction on Pure CCK-8 Standard and on
`CCK-like Immunoreactivity in Porcine Neutral Brain Extracts
`Percent of Eluate in Each Peak"
`First
`Second
`Third
`
`. I
`
`Conditions
`Oxidation of st~n,farcl
`CCK-8
`CCK-8 + 0.1 M H20 2 (15 min)
`CCK-8 + 0.1 M H20 2 (30 min)
`CCK-8 + 1.0 M H,02 (45 min)
`Reduction of oxidized standard
`CCK-8 + DTT (20 hr)
`CCK-8 + DTT (40 hr)
`CCK-8 + DTT (90 hr)
`Reduction of oxidized extract
`Neutral brain extract
`Neutral brain extract + DTT (20 hr)
`Neutral brain extract+ DTT (40 hr)
`Prevention of oxidation
`Brain tissue extracted in DTT
`0
`0
`100
`"The first, second, and third peaks correspond to the peptide with two, one, or _no oxidized
`methionine residues, respectively; the HPLC retention tirnes for these peaks were 7; 10, and 16
`min, respectively.
`
`4
`4
`37
`96
`
`0
`0
`4
`
`0
`0
`0
`
`39
`55
`49
`0
`
`11
`10
`5
`
`34
`II
`3
`
`57
`41
`14
`4
`
`89
`90
`91
`
`66
`89
`97
`
`571
`
`
`
`
`

`

`572
`
`ANNAI.S NEW YORK ACADEMY OF SCIENCF.S
`
`TABLE 2. Effect of Oxidation and Reduction on Pure CCK-33 Standard and on
`CCK-like Immunoreactivity in Porcine Acid Duodenal Extracts
`.,., ,··•1,
`Percent of Eluate in Each Peak"
`Conditio'iis
`•
`First
`Second
`Third
`Oxidation of Standard
`CCK-33
`CCK-33 0.1 M H 20 2 (15 min)
`CCK-33 0.1 M Hi02 (30 min) .
`CCK-33 1.0 M Hp2 (45 min)
`Reduction of oxidized standard
`CCK-33 + DDT (20 hr)
`CCK-33 + OTT (40 hr)
`CCK-33 + OTT (90 hr)
`Reduction of oxidized extract
`Acid duodenal extract
`Acid duodenal extract + OTT (20 hr)
`Acid duodenal extract + DTT (40 hr)
`Prevention of oxidation
`Duodenal tissue extracted in OTT
`3
`0
`97
`0
`•T