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Cerebrospinal fluid (CSF) and peptide hormones
230
T I P S - M a y 1983
which so militates against drugs of this kind. Lasagna advocates the establishment of a de facto exclusivity arrangement for orphan drugs, with the period of patent protection starting at the moment of marketing. This would give the developer a reasonable chance to recover at least his development costs. Pressure groups, representing the interests of the small numbers of patients
who suffer from the failure of orphan drugs to reach them, also have an important role in lobbying politicians and society at large to make them aware of this, to say the least, unsatisfactory situation. This is an unusual book, the thirteenth volume in a series entitled 'Drugs and the Pharmaceutical Sciences'. Although not devoted to technical scientific matters, it
draws attention to a subject too often forgotten or ignored, and it may eventually prove to be one of the most important of the series.
CSF and BBB
appear to be richly supplied with peptides. In the pigeon, for example, neurophysin and vasotocin are found in the median eminence, the neural lobe, the organum vasculosum of the lamina terminalis and the subfornical organ. In mammals, tanycytes, cells characteristic of CVOs, have been associated with luteinizing hormone- • releasing hormone, particularly in the organum vasculosum of the lamina terminalis. The presence of such peptides closely associated with CVOs, does not, however, establish a role within the CSF. Using radioimmunoassay techniques, many peptides have been identified in the CSF and the latter half of the book is concerned with such peptides. Among those detailed are vasopressin, oxytocin,
neurophysin, a-melanocyte- stimulating hormone, prolactin, sleep factor and vasoactive intestinal polypeptide. In general, evidence is presented to suggest that the CSF acts as a means of transport for peptides to reach their various sites of action. The discussions on the many questions and implications associated with such a hypothesis, however, at least reveals that this book provides a valuable insight into the mysterious, other side of the BBB.
Cerebrospinal Fluid (CSF) and Peptide Hormones edited by E. M. Rodriguez and T]. B. van Wimersma Greidanus, S. Karger 1981. •SFr 132.-/DM 158.-/US$79.25 (viii + 220pages) I S B N 3 8055 2823 X. The existence of a blood--brain barrier (BBB) and the protection thus afforded to the brain has long been recognized. The function, however, of the cerebrospinal fluid (CSF) on the other side of that barrier, which has free access to brain tissue, is far from understood. Do brain cells, for example, secrete materials into the CSF for metabolic purposes, to be washed away and hence removed from the environment of the cell? Alternatively, should such a secretion be viewed as the release of a hormone, to be taken to a distant site by the CSF and there to exert a biological action? Why are there structural modifications in some regions of the cerebral ventricular system where there is no BBB and free exchange between blood and CSF may occur? Although such questions are not answered conclusively by the present book, the fact that it addresses such questions at all and, further, draws on recent evidence with peptides to illustrate and hypothesize, makes the book of considerable interest. The f'wst half of the book supplies detailed information on the organization and structure of the cerebral ventricular system. Within this organization, particular attention is focused on those specialized areas, the circumventricular organs (CVOs), where shifting of the endothelial tight junctions from the vascular to the ventricular side has resulted in a blood-CSF barrier rather than a BBB. Besides the morphological characteristics of CVOs, a possible physiological role of one such organ, the subfornical organ, is presented. Intravenous angiotensin II elicits drinking in many species. Autoradiographic studies have shown that, whereas blood-boroe angiotensin crosses neither the BBB nor the blood--CSF barrier, it has free access to the subfornical organ. On ablation of this area, the drinking response to intravenous angiotensin is abolished. Many CVOs
Blood pressure control
PAULTURNER The author is Professor and Chairman of the Department of Clinical Pharmacology of St Bartholomew's Hospital, London, UK.
T.W.S~H The author is Section Leader in the Department of Pharmacology, Wellcome Research Laboratories, Beckenham, UK.
proteins (renins, angiotensin-converting enzyme, kallikreins); the enzymes which promote the release of the short peptides (angiotensins, kinins); and the active comBiochemical Regulation of Blood Pressure ponents of the systems. The cellular sites of action of the peptides; the receptors; and edited by Richard L. Softer, John Wiley the intracellular systems that are able to and Sons, 1981. £34.65 (viii + 456 transfer the message of the vasoconstrictor pages) I S B N 0 471 05600 6 or vasodilator peptides to the vascular This book consists of 13 review articles by smooth muscle are also analysed. Emphasis leading scientists. The editor has succeeded has been given to the renin-angiotensin sysin organizing the chapter contents in such a tem, whose history retraces the major way that it makes the book read as a coher- trends of the therapeutic achievements on ent whole. Half of the book is dedicated to hypertension since 1960. Isolation and the renin--angiotensin system (section 1), purification of the two major enzymes acthe other half to catecholamines, kinins, tivating the system, the renin and the. prostaglandins (sections 2, 3 and 4) and the angiotensin-converting enzyme, are book is concluded by a concise review (sec- described, together with the inhibitors of tion 5), in which John Laragh analyses the both enzymes, particularly those of the pathogenetic and clinical implications of converting enzyme, which are today among catecholamines and of the renin-angioten- the most potent, selective, and perhaps sin system. A carefully prepared author innocuous antihypertensive drugs. Unforindex pays a just tribute to the numerous tunately, an important group of new scientists that have contributed to the field. molecules, the antagonists of angiotensin, The various authors have succeeded in have simply been forgotten. presenting reviews on the current state of In addition to data on peptides, the reader research, and not just a summary of their finds a careful description of catecholamine personal contributions. In simple and clear synthesis, storage, release, disposition and terms for the medical profession, and metabolism, as well as a very careful deeply enough for the specialist, practically analysis of adrenergic receptors and their. all the biochemical factors implicated in the roles in the regulation of blood pressure. A regulation of blood pressure have been long chapter is also dedicated to the carefully analysed. These include large pro- mechanism of action of catecholamines tein substrates and precursors (angioten- and m particular to the catecholaminesinogens, kininogens); smaller catalytic stimulated adenylate cyclase. No mention,
T I P S - M a y 1983
which so militates against drugs of this kind. Lasagna advocates the establishment of a de facto exclusivity arrangement for orphan drugs, with the period of patent protection starting at the moment of marketing. This would give the developer a reasonable chance to recover at least his development costs. Pressure groups, representing the interests of the small numbers of patients
who suffer from the failure of orphan drugs to reach them, also have an important role in lobbying politicians and society at large to make them aware of this, to say the least, unsatisfactory situation. This is an unusual book, the thirteenth volume in a series entitled 'Drugs and the Pharmaceutical Sciences'. Although not devoted to technical scientific matters, it
draws attention to a subject too often forgotten or ignored, and it may eventually prove to be one of the most important of the series.
CSF and BBB
appear to be richly supplied with peptides. In the pigeon, for example, neurophysin and vasotocin are found in the median eminence, the neural lobe, the organum vasculosum of the lamina terminalis and the subfornical organ. In mammals, tanycytes, cells characteristic of CVOs, have been associated with luteinizing hormone- • releasing hormone, particularly in the organum vasculosum of the lamina terminalis. The presence of such peptides closely associated with CVOs, does not, however, establish a role within the CSF. Using radioimmunoassay techniques, many peptides have been identified in the CSF and the latter half of the book is concerned with such peptides. Among those detailed are vasopressin, oxytocin,
neurophysin, a-melanocyte- stimulating hormone, prolactin, sleep factor and vasoactive intestinal polypeptide. In general, evidence is presented to suggest that the CSF acts as a means of transport for peptides to reach their various sites of action. The discussions on the many questions and implications associated with such a hypothesis, however, at least reveals that this book provides a valuable insight into the mysterious, other side of the BBB.
Cerebrospinal Fluid (CSF) and Peptide Hormones edited by E. M. Rodriguez and T]. B. van Wimersma Greidanus, S. Karger 1981. •SFr 132.-/DM 158.-/US$79.25 (viii + 220pages) I S B N 3 8055 2823 X. The existence of a blood--brain barrier (BBB) and the protection thus afforded to the brain has long been recognized. The function, however, of the cerebrospinal fluid (CSF) on the other side of that barrier, which has free access to brain tissue, is far from understood. Do brain cells, for example, secrete materials into the CSF for metabolic purposes, to be washed away and hence removed from the environment of the cell? Alternatively, should such a secretion be viewed as the release of a hormone, to be taken to a distant site by the CSF and there to exert a biological action? Why are there structural modifications in some regions of the cerebral ventricular system where there is no BBB and free exchange between blood and CSF may occur? Although such questions are not answered conclusively by the present book, the fact that it addresses such questions at all and, further, draws on recent evidence with peptides to illustrate and hypothesize, makes the book of considerable interest. The f'wst half of the book supplies detailed information on the organization and structure of the cerebral ventricular system. Within this organization, particular attention is focused on those specialized areas, the circumventricular organs (CVOs), where shifting of the endothelial tight junctions from the vascular to the ventricular side has resulted in a blood-CSF barrier rather than a BBB. Besides the morphological characteristics of CVOs, a possible physiological role of one such organ, the subfornical organ, is presented. Intravenous angiotensin II elicits drinking in many species. Autoradiographic studies have shown that, whereas blood-boroe angiotensin crosses neither the BBB nor the blood--CSF barrier, it has free access to the subfornical organ. On ablation of this area, the drinking response to intravenous angiotensin is abolished. Many CVOs
Blood pressure control
PAULTURNER The author is Professor and Chairman of the Department of Clinical Pharmacology of St Bartholomew's Hospital, London, UK.
T.W.S~H The author is Section Leader in the Department of Pharmacology, Wellcome Research Laboratories, Beckenham, UK.
proteins (renins, angiotensin-converting enzyme, kallikreins); the enzymes which promote the release of the short peptides (angiotensins, kinins); and the active comBiochemical Regulation of Blood Pressure ponents of the systems. The cellular sites of action of the peptides; the receptors; and edited by Richard L. Softer, John Wiley the intracellular systems that are able to and Sons, 1981. £34.65 (viii + 456 transfer the message of the vasoconstrictor pages) I S B N 0 471 05600 6 or vasodilator peptides to the vascular This book consists of 13 review articles by smooth muscle are also analysed. Emphasis leading scientists. The editor has succeeded has been given to the renin-angiotensin sysin organizing the chapter contents in such a tem, whose history retraces the major way that it makes the book read as a coher- trends of the therapeutic achievements on ent whole. Half of the book is dedicated to hypertension since 1960. Isolation and the renin--angiotensin system (section 1), purification of the two major enzymes acthe other half to catecholamines, kinins, tivating the system, the renin and the. prostaglandins (sections 2, 3 and 4) and the angiotensin-converting enzyme, are book is concluded by a concise review (sec- described, together with the inhibitors of tion 5), in which John Laragh analyses the both enzymes, particularly those of the pathogenetic and clinical implications of converting enzyme, which are today among catecholamines and of the renin-angioten- the most potent, selective, and perhaps sin system. A carefully prepared author innocuous antihypertensive drugs. Unforindex pays a just tribute to the numerous tunately, an important group of new scientists that have contributed to the field. molecules, the antagonists of angiotensin, The various authors have succeeded in have simply been forgotten. presenting reviews on the current state of In addition to data on peptides, the reader research, and not just a summary of their finds a careful description of catecholamine personal contributions. In simple and clear synthesis, storage, release, disposition and terms for the medical profession, and metabolism, as well as a very careful deeply enough for the specialist, practically analysis of adrenergic receptors and their. all the biochemical factors implicated in the roles in the regulation of blood pressure. A regulation of blood pressure have been long chapter is also dedicated to the carefully analysed. These include large pro- mechanism of action of catecholamines tein substrates and precursors (angioten- and m particular to the catecholaminesinogens, kininogens); smaller catalytic stimulated adenylate cyclase. No mention,