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Cholecystokinin (CCK) in the nervous system (Ellis Horwood health science series)
185
Cholecystok&in (CCK) in the Nervous System (Ellis Horwood Health Science Series) J. de Belleroche and G.J. Dockray (Eds.) Verlag Chemie, Weinheim, 1984 132 pp., DM 76.00, ISBN (intern.) 0-87573-369-2/3-572-26223-7 A decade has passed since Vanderhaegen, Signeau and Gepts discovered gastrin-like immunoreactivity in the central nervous system. The immunoreactive material had an inhomogeneous distribution with the "highest concentrations in cortical grey matter" and was subsequently identified as the C-terminal octapeptide of cholecystokinin. During this decade, peptides of the CCK family have been implicated in a wide variety of CNS functions, ranging from production of satiety to antinociception and involvement in the pathophysiology of schizophrenia. Here is a book which claims to summarize current knowledge about CCK peptides in the nervous system, spanning from the molecular events of precursor processing to behavioural actions in the whole animal. The book contains contributions of several of the most productive workers in this field. The book is composed of three sections. The first of these, called 'Molecular forms of CCK and biosynthesis', includes Dockray and Rehfeld among the authors and deals with the cellular processing of different peptides of the CCK family and their identification. Many valuable methodological considerations are given, including different extraction procedures that have proven to be efficient for the various forms of the peptides. CCK fragments other than sulphated CCK-8 seem to constitute 1050% of the CCK-like immunoreactivity. The physiological significance of these other fragments is not discussed. The second section is called 'CCK distribution in the brain'. It starts with an excellent chapter by Beinfeld and Palkovits, which brings into a relative order the complicated anatomy of known CCK pathways. Of course, the 'meso-limbic' CCK-DA connection of H6kfelt attracts interest, and the authors emphasize the important, but often over-looked fact that not all CCK in Nc. accumbens comes from the ventral tegmental area together with DA, and that not all CCK neurons in the VTA project to the accumbens. Also, the hypothalamo-pituitary connection is described, as is the hippocampo-septal projection. Here, the old dogma that only pyramidal neurons project out of the hippocampus is contradicted. In the field of neuropeptide research, no dogmas are safe ... In the first chapter of the last section, called 'Mechanisms of action of CCK', Kelly and Brooks review the electrophysiological evidence for a neurotransmittor role of CCK. CCK is excitatory on neurons in many structures, including the myenteric plexus, hippocampus, cerebral cortex, substantia nigra, the ventral tegmentum, and the dorsal horn of the spinal cord. When applied with sufficient speed and in proper amounts, the excitatory response to CCK is as fast, if not faster, than that to glutamate. Interestingly, the resultant excitation seems to be TTX-resistent. It is tempting to speculate with the authors that slow Ca 2 +-currents are involved in the excitation, but, as is pointed out, Ca 2 +-free/high Mg 2 +-media have failed to alter the
186 excitatory effect on isolated spinal cord preparations. The question is a crucial one for all peptide research. Of course, speculations about the role of Ca 2 + and Ca 2 +-operated ion channels as mediators of CCK effects have been inspired by the brilliant patch-clamp studies performed on pancreatic acinar cells by Petersen. These are reviewed by himself in the next chapter. The results are so interesting that it is difficult to keep in mind the important reservation that the mode of action of CCK in the CNS might be totally different from that in pancreatic acini. In a final chapter, Sheehan and Belleroche discuss the antinociceptive, hypothermic, sedative, satiety-producing and anti-convulsive effects of CCK peptides and the possible neurochemical mechanisms underlying some of these behavioural effects. The focus is on modulation of release of GABA and DA. The results must be interpreted with caution, as most of them are obtained with the CCK-analogue caerulein rather than with CCK itself. The book makes good reading and will probably serve as a reference work on CCK in the brain for some years to come. CCK is, perhaps together with substance P, the peptide which has been most widely studied in its new-found role as neurotransmitter (or neuromodulator). For that reason, it is something of a model substance for all of us who wish to clarify the function of neuropeptides in the CNS. Markus Heilig Department of Pharmacology University of Lund Lund, Sweden
Cholecystok&in (CCK) in the Nervous System (Ellis Horwood Health Science Series) J. de Belleroche and G.J. Dockray (Eds.) Verlag Chemie, Weinheim, 1984 132 pp., DM 76.00, ISBN (intern.) 0-87573-369-2/3-572-26223-7 A decade has passed since Vanderhaegen, Signeau and Gepts discovered gastrin-like immunoreactivity in the central nervous system. The immunoreactive material had an inhomogeneous distribution with the "highest concentrations in cortical grey matter" and was subsequently identified as the C-terminal octapeptide of cholecystokinin. During this decade, peptides of the CCK family have been implicated in a wide variety of CNS functions, ranging from production of satiety to antinociception and involvement in the pathophysiology of schizophrenia. Here is a book which claims to summarize current knowledge about CCK peptides in the nervous system, spanning from the molecular events of precursor processing to behavioural actions in the whole animal. The book contains contributions of several of the most productive workers in this field. The book is composed of three sections. The first of these, called 'Molecular forms of CCK and biosynthesis', includes Dockray and Rehfeld among the authors and deals with the cellular processing of different peptides of the CCK family and their identification. Many valuable methodological considerations are given, including different extraction procedures that have proven to be efficient for the various forms of the peptides. CCK fragments other than sulphated CCK-8 seem to constitute 1050% of the CCK-like immunoreactivity. The physiological significance of these other fragments is not discussed. The second section is called 'CCK distribution in the brain'. It starts with an excellent chapter by Beinfeld and Palkovits, which brings into a relative order the complicated anatomy of known CCK pathways. Of course, the 'meso-limbic' CCK-DA connection of H6kfelt attracts interest, and the authors emphasize the important, but often over-looked fact that not all CCK in Nc. accumbens comes from the ventral tegmental area together with DA, and that not all CCK neurons in the VTA project to the accumbens. Also, the hypothalamo-pituitary connection is described, as is the hippocampo-septal projection. Here, the old dogma that only pyramidal neurons project out of the hippocampus is contradicted. In the field of neuropeptide research, no dogmas are safe ... In the first chapter of the last section, called 'Mechanisms of action of CCK', Kelly and Brooks review the electrophysiological evidence for a neurotransmittor role of CCK. CCK is excitatory on neurons in many structures, including the myenteric plexus, hippocampus, cerebral cortex, substantia nigra, the ventral tegmentum, and the dorsal horn of the spinal cord. When applied with sufficient speed and in proper amounts, the excitatory response to CCK is as fast, if not faster, than that to glutamate. Interestingly, the resultant excitation seems to be TTX-resistent. It is tempting to speculate with the authors that slow Ca 2 +-currents are involved in the excitation, but, as is pointed out, Ca 2 +-free/high Mg 2 +-media have failed to alter the
186 excitatory effect on isolated spinal cord preparations. The question is a crucial one for all peptide research. Of course, speculations about the role of Ca 2 + and Ca 2 +-operated ion channels as mediators of CCK effects have been inspired by the brilliant patch-clamp studies performed on pancreatic acinar cells by Petersen. These are reviewed by himself in the next chapter. The results are so interesting that it is difficult to keep in mind the important reservation that the mode of action of CCK in the CNS might be totally different from that in pancreatic acini. In a final chapter, Sheehan and Belleroche discuss the antinociceptive, hypothermic, sedative, satiety-producing and anti-convulsive effects of CCK peptides and the possible neurochemical mechanisms underlying some of these behavioural effects. The focus is on modulation of release of GABA and DA. The results must be interpreted with caution, as most of them are obtained with the CCK-analogue caerulein rather than with CCK itself. The book makes good reading and will probably serve as a reference work on CCK in the brain for some years to come. CCK is, perhaps together with substance P, the peptide which has been most widely studied in its new-found role as neurotransmitter (or neuromodulator). For that reason, it is something of a model substance for all of us who wish to clarify the function of neuropeptides in the CNS. Markus Heilig Department of Pharmacology University of Lund Lund, Sweden