- Email: [email protected]
Pharmacology in the molecular age
BOOK REVIEWS
TIBS 24 – APRIL 1999
imbalance and inconsistencies of presentation are a minor irritation to the reader. Some chapters are methodological in a practical sense, giving informative protocols; others seem more keen to discuss results. Some concentrate on details such as the manufacturer of the balance or actually instruct the reader to use a beaker; by contrast, others tell us to carry out methods ‘as per cited reference’. Figures that are uninformative and unexplained are presented. We are told in the preface that protocols in routine use are not included – this is a surprising statement, considering the number of routine assays presented. Some chapters could have been written five years ago; others describe useful applicable methods of crucial immediate interest (e.g. the quantification of 8hydroxy-2-deoxyguanosine) but without addressing the current major concerns –
such as how DNA is protected from oxidation during extraction and digestion. The references to the work of Cadet and Dizdaroglu are reassuring, but the lack of recent references to such a developing area is surprising. Not all chapters clearly describe how to obtain results from the methods proposed, but maybe this was not the intention. In some instances, calibration of methods or validation of assays, reproducibility and precision are not discussed. Given that the book intended to focus on HPLC assays, purity of standards for HPLC analyses would have been very valuable information, especially for the carotenoids. One might anticipate that authors that have the appropriate expertise and a track-record in the application of such techniques were selected to contribute to this text. Indeed, one might expect that
authors would refer to a number of their own publications in which they apply the assay concerned. Several chapters refer to no relevant articles by the authors themselves! Thus, the emergence of the book from a ‘1993 international conference on the use of free radical assays in diagnostic medicine’ (according to the preface) has not translated well into a book on the state-of-the-art methodology on the eve of the 21st century. Rather, it is a very mixed bag of protocols in terms of standard of presentation and usefulness.
Pharmacology in the molecular age
One of the initial volumes in this series is Identification and Expression of G Protein-Coupled Receptors, which is edited by Kevin R. Lynch. Chapters contributed by leading experts in homology- and PCRbased receptor cloning, expression cloning, and heterologous expression in mammalian cells, bacteria, Xenopus oocytes, insect cells and yeast make this volume a first-class reference source for those contemplating entering this competitive research arena. The chapters are written and use state-of-the-art research findings to illustrate and complement the description of current research methods. As such, the book is interesting and informative reading, often giving useful tips on how to avoid the artifactual findings that can complicate the interpretation of cloning and expression experiments – findings that one suspects were hard lessons learned by the authors. Several chapters discuss methods for high-density receptor expression that will facilitate the purification and reconstitution of GPCRs. Clearly, the production of large quantities of receptor protein is a prerequisite for the biophysical study of these proteins that will be required to understand and appreciate fully the plentiful mutagenesis data that have guided the current generation of GPCR receptor models. One particularly useful contribution, authored by the editor himself, details methods for searching protein sequence, nucleotide sequence and EST databases for novel GPCR-family members. The reader is provided with a quick summary of the most-useful current databases and search programs, as well as numerous URLs of websites that provide summary information on receptor structure,
mutagenesis and receptor family trees. The stage set with this backdrop, the author then briefly describes the current state of research in what surely will be the most challenging receptor pharmacological problem of the next five years: the identification of ligands and the determination of the physiological roles of the growing number of GPCR-family orphan sequences. However, one disappointment is the near-total lack of discussion of probe design in these silicon-based cloning experiments – given that the success of these methodologies is totally dependent on this design choice. In summary, if this volume is any indication, the new Receptor Biochemistry and Methodology Series will be a welcome addition to the pharmacology library, and the subsequent volumes of this series should be eagerly awaited.
Identification and Expression of G Protein-Coupled Receptors edited by Kevin R. Lynch, Wiley-Liss, 1998. £100.00 (xii 1 222) ISBN 0 471 18310 5 The application of molecular techniques to the study of receptor and ion-channel pharmacology began in the mid-1980s and has revolutionized the study of signalling molecules. For one major receptor family, the molecular cloning of the b2 adrenergic receptor in 1986 ushered in a new era in the study of what are now known as G-proteincoupled receptors (GPCRs). Since then, >100 novel genes that encode members of this receptor superfamily have been identified, revealing a previously unsuspected complexity in the pharmacology of the myriad of hormones, neurotransmitters, neuropeptides, glycoproteins, immunoinflammatory modulators and lipids that activate and modulate these receptors. The rapid expansion of this field has provided a decade of exciting breakthrough discoveries by both academic and pharmaceuticalindustry scientists alike, and the rate of discovery of new receptors and their ligands shows no signs of abating in the near future. It is in this context that the reintroduction of the Receptor Biochemistry and Methodology Series by Wiley-Liss Publishers under the the editorship of David R. Sibley and Catherine D. Strader is a welcome addition to the growing literature in this productive research area.
162
CATHERINE RICE-EVANS International Antioxidant Research Centre, The Guy’s, King’s College and St Thomas’s School of Biomedical Sciences, King’s College – Guy’s Campus, St Thomas’s St, London, UK SE1 9RT.
MARGARET A. CASCIERI Dept of Molecular Pharmacology/Immunology and Rheumatology, Merck Research Laboratories, Rahway, NJ 07065, USA.
Author correction In the February 1999 issue, we published an obituary of Professor Samuel Weiss (TiBS 24, 45 – 46). In the article title and the figure legend, the authors refer to him as Samuel D. Weiss. He was in fact Samuel B. Weiss.
TIBS 24 – APRIL 1999
imbalance and inconsistencies of presentation are a minor irritation to the reader. Some chapters are methodological in a practical sense, giving informative protocols; others seem more keen to discuss results. Some concentrate on details such as the manufacturer of the balance or actually instruct the reader to use a beaker; by contrast, others tell us to carry out methods ‘as per cited reference’. Figures that are uninformative and unexplained are presented. We are told in the preface that protocols in routine use are not included – this is a surprising statement, considering the number of routine assays presented. Some chapters could have been written five years ago; others describe useful applicable methods of crucial immediate interest (e.g. the quantification of 8hydroxy-2-deoxyguanosine) but without addressing the current major concerns –
such as how DNA is protected from oxidation during extraction and digestion. The references to the work of Cadet and Dizdaroglu are reassuring, but the lack of recent references to such a developing area is surprising. Not all chapters clearly describe how to obtain results from the methods proposed, but maybe this was not the intention. In some instances, calibration of methods or validation of assays, reproducibility and precision are not discussed. Given that the book intended to focus on HPLC assays, purity of standards for HPLC analyses would have been very valuable information, especially for the carotenoids. One might anticipate that authors that have the appropriate expertise and a track-record in the application of such techniques were selected to contribute to this text. Indeed, one might expect that
authors would refer to a number of their own publications in which they apply the assay concerned. Several chapters refer to no relevant articles by the authors themselves! Thus, the emergence of the book from a ‘1993 international conference on the use of free radical assays in diagnostic medicine’ (according to the preface) has not translated well into a book on the state-of-the-art methodology on the eve of the 21st century. Rather, it is a very mixed bag of protocols in terms of standard of presentation and usefulness.
Pharmacology in the molecular age
One of the initial volumes in this series is Identification and Expression of G Protein-Coupled Receptors, which is edited by Kevin R. Lynch. Chapters contributed by leading experts in homology- and PCRbased receptor cloning, expression cloning, and heterologous expression in mammalian cells, bacteria, Xenopus oocytes, insect cells and yeast make this volume a first-class reference source for those contemplating entering this competitive research arena. The chapters are written and use state-of-the-art research findings to illustrate and complement the description of current research methods. As such, the book is interesting and informative reading, often giving useful tips on how to avoid the artifactual findings that can complicate the interpretation of cloning and expression experiments – findings that one suspects were hard lessons learned by the authors. Several chapters discuss methods for high-density receptor expression that will facilitate the purification and reconstitution of GPCRs. Clearly, the production of large quantities of receptor protein is a prerequisite for the biophysical study of these proteins that will be required to understand and appreciate fully the plentiful mutagenesis data that have guided the current generation of GPCR receptor models. One particularly useful contribution, authored by the editor himself, details methods for searching protein sequence, nucleotide sequence and EST databases for novel GPCR-family members. The reader is provided with a quick summary of the most-useful current databases and search programs, as well as numerous URLs of websites that provide summary information on receptor structure,
mutagenesis and receptor family trees. The stage set with this backdrop, the author then briefly describes the current state of research in what surely will be the most challenging receptor pharmacological problem of the next five years: the identification of ligands and the determination of the physiological roles of the growing number of GPCR-family orphan sequences. However, one disappointment is the near-total lack of discussion of probe design in these silicon-based cloning experiments – given that the success of these methodologies is totally dependent on this design choice. In summary, if this volume is any indication, the new Receptor Biochemistry and Methodology Series will be a welcome addition to the pharmacology library, and the subsequent volumes of this series should be eagerly awaited.
Identification and Expression of G Protein-Coupled Receptors edited by Kevin R. Lynch, Wiley-Liss, 1998. £100.00 (xii 1 222) ISBN 0 471 18310 5 The application of molecular techniques to the study of receptor and ion-channel pharmacology began in the mid-1980s and has revolutionized the study of signalling molecules. For one major receptor family, the molecular cloning of the b2 adrenergic receptor in 1986 ushered in a new era in the study of what are now known as G-proteincoupled receptors (GPCRs). Since then, >100 novel genes that encode members of this receptor superfamily have been identified, revealing a previously unsuspected complexity in the pharmacology of the myriad of hormones, neurotransmitters, neuropeptides, glycoproteins, immunoinflammatory modulators and lipids that activate and modulate these receptors. The rapid expansion of this field has provided a decade of exciting breakthrough discoveries by both academic and pharmaceuticalindustry scientists alike, and the rate of discovery of new receptors and their ligands shows no signs of abating in the near future. It is in this context that the reintroduction of the Receptor Biochemistry and Methodology Series by Wiley-Liss Publishers under the the editorship of David R. Sibley and Catherine D. Strader is a welcome addition to the growing literature in this productive research area.
162
CATHERINE RICE-EVANS International Antioxidant Research Centre, The Guy’s, King’s College and St Thomas’s School of Biomedical Sciences, King’s College – Guy’s Campus, St Thomas’s St, London, UK SE1 9RT.
MARGARET A. CASCIERI Dept of Molecular Pharmacology/Immunology and Rheumatology, Merck Research Laboratories, Rahway, NJ 07065, USA.
Author correction In the February 1999 issue, we published an obituary of Professor Samuel Weiss (TiBS 24, 45 – 46). In the article title and the figure legend, the authors refer to him as Samuel D. Weiss. He was in fact Samuel B. Weiss.