Cerebral blood flow and metabolism

TjPS - July 1993 IV& 241 contributing data shown.

to the experimental

References 1 Berridge, M. J. (1993) Natztre 361, 315-325 2 Nishizuka, Y. (1992) SC~CJZCP 258, 607-614 3 Rhee, S. G. and Choi, K. D. (1992) I. Biol. Chem. 267,12393-12396 4 Cockcroft, 5. and Thomas, G. M. H. (1992) Biockem. j. 288, l-14 5 Nahorski, ‘5. R. and Challiss, R. A. J. (1991) Neurocl~em. hrt. 19. 207-212 6 Dohiman, H. G., Tho&er, J., Caron, M. G. and Lefkowitz, R. J. (1991) Attntc. Rev. Biffchel~. 60, 653~6t$ 7 Benidge, M. J., Downes, C. P. and Hanley, M. R. (1982) ~~~c~e~~. I. 206, 587-595 8 Nakahata, N. and Harden, T. K. (1987) Biochem. ].241,337-344 9 Thompson, A. K. and Fisher, S. K. (1990) J. Pharmacol. Exp. Ther. 252, 744-752 10 Pearce, 3.. Morrow. C. and Muruhv, S. (1988) J. Neurockem. X1,936-944’ ’ 11 Eva, C., Gamalero, S. R., Genazzani, E. and Costa, E. 0990) J. Pkarmacof. Exp. Ther. 253,257-265 12 Stauderman. K. A. and Pruss, R. M. (1990) 1. Ne&ochem. 54‘946-953 13 Balla, T., Baukal, A. J., Guillemette, G. and Catt, K. J. (1988) 1. Biol. Chem. 263, 4083-4091

Tackling-tie-jungle book Cerebral Blood Flow and Metabolism by Lars Edvinsson, Eric .T. MacKenzie and lames McCulloch, Raven Press, 2993. $262.50 lix + 683 pages) 1SBN 0 88 167 918 6 This book is a monograph covering a difficult subject that is littered with discrepant and, at data. The times, inappropriate authors quote in their preface Roy and Sherrington [J. Physiol. (Lorzd.) (1890) 11, 8%1081, who a century ago stated: ‘One marked characteristic of the literature dealing with the cerebral circulation is, we think, the contradictory nature of the results which have been obtained by different investigators. There is no reason, we imagine, for doubting that the cause of these discrepancies is to be found in the great difficulty of avoiding the sources of error which plentifully surround the subject, and in

285 14 Hulme, E. C., Birdsall, N. J. M. and Buckley, N. I. (1990) AJIJZ~~. Rru. PRarmncol. Toxicul. 30, 633-673 15 Wail, S. J.. Yasuda. R. P., Li, M. and Wolfe, 6. E. (1991) Mol. Pkarmacol. 40, 783-789 16 Suniva, H.. Tennes. K. A. and Putnev. 1. I?‘.; Jr (1987) gjoc~?e~7~.1. 244, 647-65: 17 Menniti, F. S., Takemura, H., Oliver, K. G. and Putney, J. W., jr(1991) Mot: Pkarmacol. 40, 727-733 18 Dillon-Carter, 0. and Chuang, D-M. (1989) J. Neurochent, 52, 598-603 19 Kassis, S. and Fishman, P. H. (1984) Proc. Nntt Acad. Sci. USA 81,6686-6690 20 Hausdorff, W. P., Caron, M. G. and Lefkowitz, R. J. (1990) FASEB f. 4, 2881-2889 21 Roth, N. S., Campbell, P. T,, Caron, M. G., Lefkowitz, R. J. and Lohse, M. J. (1991) Proe. N&l Acad. Sci. USA 88, 6201-6204 22 Tobin, A. B. and Nahorski, S. R. (1993) J, Biol. Chem. 268,9617-9823 23 Leeb-Lundberg, L. M. F., Cotecchia, S., DeBlasi, A., Caron, M. G. and Lefkowitz, R. J. (1987) 1. Biuf. Ckem. 262, 3098-3105 24 Khaeppelberg, U. G., Gates, L. K., Goretick, F. S. and Miller, L. J. 11991) J, Biot. Ckem. 266, 2403-2408 2s Berstein, G. et al. (1992) Ceil 70,411-418 26 Lambert, D. G., Challiss, R. A. J. and Nahorski, S. R. (1991) Bioclzem. J. 273, 791-794 27 Fowler, C. J, and Tiger, G. (1991) Neuro-

cketn. Inr. 19, 171-206 28 Eberhard, D. A. and Hoiz, R. W. (1988) Trends Neurosci. 11, 517-520 29 Meldolesi, 1.‘ Clementi, E., Fasoiato, C., Zacchetti, D. and Pozzan, T. (1991) Trends PharJ~za~~l.Sci. 12, 289-292 30 Fisher, S. K.. Domask, L. M. and Roland, R. M. (1989) Mol. Plz~r~lacff~. 35,195-204 31 Tobin, A. B., Lambert, D. G. and Nahorski, S. R. (1993) iWal. Pharmacol. 42,1042-1048 32 Cheek, T. R. (1991) Pkannac. Tker. 52, 173-189 33 Mulfaney, I., Dodd, M. W., Buckley, N. and MilliRan, G. (19931 Biockem. I. 289. 125-131 34 Lameh, J. et al. (1992) f. Biot. Ckem. 267, 13406-13412 35 Wojcikiewicz, R. J. H. and Nahorski, S. R. (19%) I. Biot. Chem. 266, 22234-22241 36 Kiley, S. C., Parker, P. J., Fabbro, D. and Jaken, S. (1991) 1. Biol. Cbem. 266, 23761-23768 . 37 Akita, Y., Ohno, S., Yajima, Y. and Suzuki, K. I199Ot B&kern. Biookus. ‘ 4 Res. Comm&. 1?2,1&#-189 38 Hepler, 1. R., Earp, H. S. and Harden, T. i<. (19sS) J. Biol:Cfiem. 263,7610-7619 39 Willems, P. H. C. M., Van Den Broek, B. A. M., Van OS, C. H. and De Pont, J. J. H. H. M. (1989) J. Biof. Ckem. 264, 9762-9767 40 Wojcikiewicz, R. J. H., Nakade, S., Mikoshiba, K. and Nahorski, S. R. (1992) J. Neurockem. 59,383386

certain technical overcoming difficulties which we shall have to refer to. The ease with which one can obtain results upon certain points, on taking up the subject, is itself, we believe, apt to make the inquirer careless in controlling sources of error, which, it may be noted, are some of them not at first sight obvious. We must on this account say more about the technology of our subject than would be necessary were the subject a simpler one’. The authors and I are in complete agreement that ‘these words are as pertinent today as they were in 1890’. However, having said this, I believe that the authors have tackled the subject bravely and with finesse. The book has been skilfully divided into five parts that deal with the anatomy, physiology, fundamental pharmacology, and disordered characteristics control of the cerebral circulation. The anatomical part (90 pages) mainly deals with general and

comparative anatomy of cerebral circulation in several species as well as the characteristics of vascular wall and perivascular nerve fibres. The physiological part (45 pages) deals with certain functional aspects, covering vascular reactivity permeability, and energy generation and the nature The neu~transmission. of pharmacology part is the most extensive (300 pages) and contributes a comprehensive coverage of various biogenic substances (amines, amino acids, peptides, eicosanoids, etc.) as well as two classes of drugs (Ca*+ channel blockers and anaesthetics). The part dealing with fundamental characteristics (80 pages) includes a critical and useful analysis of the methods employed for the measurement of cerebral blood flow in both humans and animals. The last part is devoted to the discussion of some pathophysiological conditions involving cerebral circulation, such as cerebral ischaemia, stroke and migraine. The book is well conceived and clearly written and it provides upto-date and stimulating essays on different aspects of cerebral cirAation and metabolism. The

TiPS - Jut!/ 1993 [Vol. 141

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authors have succeeded in making ,I difficult subject look relatively easy and pleasant to tackle. This book would therefore be of great (neurovalue to investigators and physiologists scientists, pharmacologists) working in the field of cerebral blood flow and metabolism, as well as to clinicians (primarily neurologists and neurosurgeons) by providing essential background material. If any criticisms are to be made, they are about details only. For example, I would have found it useful if a little more attention was paid to regional variations in the chapter on the blood-brain barrier. The chapter on 5-hydroxytryptamine (5HT) could have given a

more complete account of the vascular pharmacology and receptor subtypes, and it perhaps errs in giving the impression that certain anti-migraine drugs owe their therapeutic action to blockade of 5HT2 receptors mediating cerebral vasoconstriction (but this is a hotly contested area!). Another aspect th>t may have deserved attention is the comparison of the pharmacology of intra- and extracerebral circulation. Furthermore, I believe that the readers would have been helped if each chapter was preceded by a synopsis delineating the ‘take-home’ message. Notwithstanding these points, I am extremely pleased that the authors, as revealed in the preface,

did not heed to the caution sounded by ‘more experienced who thought that colleagues’ writing this book would be a task for them to undertake when ctoser to retirement. Given their youth, it would have meant that we would have been denied the product of their intellect and wisdom for a long time. I hope that the authors will use this period and beyond for updating this excellent text at regular intervals.

Keeping PKC active

The second section of the book concentrates on how these activation characteristics might be extended to what we know of the irz viva consequences of PKC stimulation. PKC activation has been implicated in many signalling systems and, instead of trying to cover all of these, a few are examined in some depth to give the reader an idea of the problems and pitfalls of the experimental techniques available. PKC involvement in sustained cellular responses is examined, as opposed to the experimentally accessible immediate consequences of activation. The phospho~lation state of myristoylated alanine-rich C kinase substrate is often used as a marker for PKC activation in the intact cell. It serves as a good model for potential substrates as there are clues to its function in cytoskeletal reorganization, and its pattern of phospho~Iation demonstrates that PKC activity can be influenced by substrate availability at

the membrane. This is complimented by a review of the association of the isoforms of PKC with the cytoskeleton and the nucleus, highlighting the variety of alterations in cellular function ascribed to PKC activation. In a rapidly expanding field in which several papers are published every week, a book cannot hope to include up-to-the minute information. However, the book goes a long way towards providing ‘all you ever wanted to know about PKC but were afraid to ask’, by highlighting the problems and advantages of experimental techniques and relating them to carefully chosen responses. The balance achieved between reviews of different aspects of PKC and models for its activation and function has resulted in a valuable reference work.

Protein Kinase C: Current Concepts and Future Perspectives edited by David S. Lester nlld Richd M. Epnnd, Ellis Hovwood, 1992. f59.00 (xii f 365 pngesl iSBN 13 720186 9 A whole book dedicated to a single family of enzymes would appear to be an ambitious project. This book fills the gap between research papers and textbooks by providing reviews in a wide range of fields related to protein kinase C (PKC) and using the available data to put forward models for PKC activation and function. The encouraging outcome is that different authors arrive at similar conclusions from alternative viewpoints. The book is divided into two parts, the first dealing with structural and mechanistic aspects of PKC activation while the second part concentrates on potential functions. The former includes discussion of the structural requirements of the activating diacylglycerols and the basis of the Ca*+ and phospholipid dependency. The consensus reached is that association of PKC with the membrane is a specific event that can be separated from its subsequent activation. The possibilities for functional variation between the family members, deduced from the sequence divergence and limited knowledge of the differences in their biochemical properties, are also discussed.

TRAMDD R. SAXENA Dranrtmerrt of Phnrntncoloev amf Dutch M(qmirte Rcsb-ch Group, “bwdiovnscrrlnr Rescnrch Irtstitutr ‘COEUR’, Erasttttcs University Rotterdnrrr, PO Box 2738, 3000 DR Rotterdnnr, The Nethrrlmds.

TiPS Receptor Nomenclature Supplement 1993 4th Edison Additional

copies are available

from:

Kim Smith, Elsevier Trends Journals, 68 Hills Road, Cambridge, UK CB2 1LA. FAX: f44 223 321410