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Calmodulin and cell functions
TIPS -April
176
Bmks -
---
Praiseworthy
teristicssuchas milk composition, ptoduction and flow. 11ends with an attempt to relate plasma and milk ~~~i~t~ Drugs in Breast Milk profiles allowing an estimateof the amount by John T. Wilson, MTP Press Ltd. of drug receivedby the suckling child to be 1981. El 1.95 (x. + 110 pages) 15811’ 0 made. The proposed3compmhnent open t?5200 575 x model is tesfedusingappropriatedata from the literature. Sections are devoted to John Wilson has compiled a monograph specific &asses of drugs, e.g. antimicro consistingof a seriesof conttibutionswhich biis. psychoactive substancesand anticover the cunent state of knowledge very epileptic drugs, and gastrointestinaldrugs comprehensively.Tlte articlesare amutged all of which give a goodreview of the litera in logical fashion commencing with the turn. A final chapteron the consequenceof basic physiology of milk pmduction and efememmy pharmacokin&cs, progressing ro data conrming the excretion of specific compoundsinto milk and the effect of some of these xgents on the future development and behaviour of the bteast-fedinfant. The Caln~ulin and Cell Functions literature has obviously been very widely edited by D. M. Wonerson wd F. F. surveyed and many Referencesate cited Vincenti, New York Academy of making thii an ideal bibliogmphy. What Sciences, J 931. $86.00 (xii .+ 446pagesj becomesappasentftom such a work is the JS6N 0 89766 101 X obvious lock of knowledge in such an imppnantatca. Muchofthedataptcscmcd, Many of the functions of eukaryote cells as the authors constimtly remind us. were (e.g. exocytosis. contraction. the motion5 obtained from single ‘one-otr studiesand of cilia and flagellae and the pumping of fmquently from animal studies. Hence Ca*+ across membranes) are normally rhea has been extrapolation of data fmm switched on by a rise in cytosol Gas’ ion animals to man and pnerali7ations made concemMion, so cells need internal ‘Gas’ from the few human nsults. Thus, where receptors’which detect and respondto this them has for many years been much con- ionic change. The first such‘receptor’ to be cern (and study) on the effects of dntgs identified was the troponin C of skeletal .. admuwcd to the motlur during peg- muscle, but it is now widely acceptedthat nancy on tbe infant, the potential of the the main cytoplasmic ‘Gas* receptor’ in bteastas a toute for drug excretion and sub other eukaryotccclis (whether plant or pm. sequenfeffectson the infant have been very tist. testicle or tumour) is Cahnodulin, a poorly studied. small protein that is highly conserveddurThe pharmacokinetic chapter gives a ing evolution, is acidic and binds four Caa’ basictt&seonthcpropertiesgovemingthe ions. tram&r of drugs across biological mem Is a broad faith in the functional versatiG bmnes and n&sting these to milk charac- ity of this widespreadproteinju~~~~ Are lbere other, as yet unidentified(or lesspub licixed). cytoplasmicCa” receptors?How good are the tools we use to investigatethe functions of calmodulin (and hence the answersthey yield)? How com%zt,and how generally a~~~b~, m our cuncnt mechanistic models of calmodulin’s actions?Ideally. a book entitledGdmodubt and Cell Funct~~ would directly addresssuch questtons,and it might even do so in languagethat would attract a sub stantial audiince fmm the many outsiders who now find themselvestrying to join the calmodulincommunity. This beok does not achieve that ideal, probably for two reasons:the field is too young for other thanprovisionalanswersto the questions above, and this volmne
For aficionados?
J 982
_I
some of the pharmacologically active agents discussed on infant hehaviour is extremely brief with a si~n~~c~t proportion of the results being derived,ftwm sub. primate animals. The diBlculties in obtain. ing data from humansis discussed. This is an extremely useful piece of work, praiseworthy for both the contentof the i~ivid~ ~t~butio~ and the extensive natureof the referencesit provides. LIDIA J. NOTARIANNI
records the proceedings of a meeting of convinced calmodulin aficionados who have mostly written for li*& felktw club members. rfowever, it will long remain a mine of information on all &pects of calrn~~in structuteand batiks. but a mine that will only yield its richesafter considerable toil by the reader. Amongst the most intriguingnugg&i arc a variety of hintsasto importantnew diitions that work on caimodulin is taking. Examples include: the impcctanceof interactionswith ~~iphilic molecules, be they inhibitory cationic drugs such as trifhrornperaxine (almost everyone’s un~liahie(?) test for calmodu. tin’s involvementin any cellular process) or anionic activatory notGonired or ~~i~i~~ (ted cell Ca*+-ATPase in anionic lipid liposomes respondsfully IO Cax’ even without calmoduhn!); a prob. able role for catmodulin in the @armacological adjustment of dopamine recep tar sensitivitvin v&o. and the localixxtion of calmodul~ (without es~~bJ~hedfunctions) on both sides of many synapses,so that new ideas for calmoduhn function in the CNS ate emerging at the same time as Weiss’s arguments that calmodulin is a major receptor for antipsychotic dntgs stem to be fading; the identification of at least two enzymes ( I S.hydmxyprostaglandindehydmgenase and cardiac adenylate cyclase) that show calmodulin dependent inhibition by Cal’; the wide spread involvement of cabnodulin in con trol of Gas’ transportat membranes,prob. ably by severaldifferent mechanisms. To summarize, this is a useful book bur one that is, becatuseof it.. style and its very Sigh price, destinedmainly for Muaries and experts. R. H. MICHELL
176
Bmks -
---
Praiseworthy
teristicssuchas milk composition, ptoduction and flow. 11ends with an attempt to relate plasma and milk ~~~i~t~ Drugs in Breast Milk profiles allowing an estimateof the amount by John T. Wilson, MTP Press Ltd. of drug receivedby the suckling child to be 1981. El 1.95 (x. + 110 pages) 15811’ 0 made. The proposed3compmhnent open t?5200 575 x model is tesfedusingappropriatedata from the literature. Sections are devoted to John Wilson has compiled a monograph specific &asses of drugs, e.g. antimicro consistingof a seriesof conttibutionswhich biis. psychoactive substancesand anticover the cunent state of knowledge very epileptic drugs, and gastrointestinaldrugs comprehensively.Tlte articlesare amutged all of which give a goodreview of the litera in logical fashion commencing with the turn. A final chapteron the consequenceof basic physiology of milk pmduction and efememmy pharmacokin&cs, progressing ro data conrming the excretion of specific compoundsinto milk and the effect of some of these xgents on the future development and behaviour of the bteast-fedinfant. The Caln~ulin and Cell Functions literature has obviously been very widely edited by D. M. Wonerson wd F. F. surveyed and many Referencesate cited Vincenti, New York Academy of making thii an ideal bibliogmphy. What Sciences, J 931. $86.00 (xii .+ 446pagesj becomesappasentftom such a work is the JS6N 0 89766 101 X obvious lock of knowledge in such an imppnantatca. Muchofthedataptcscmcd, Many of the functions of eukaryote cells as the authors constimtly remind us. were (e.g. exocytosis. contraction. the motion5 obtained from single ‘one-otr studiesand of cilia and flagellae and the pumping of fmquently from animal studies. Hence Ca*+ across membranes) are normally rhea has been extrapolation of data fmm switched on by a rise in cytosol Gas’ ion animals to man and pnerali7ations made concemMion, so cells need internal ‘Gas’ from the few human nsults. Thus, where receptors’which detect and respondto this them has for many years been much con- ionic change. The first such‘receptor’ to be cern (and study) on the effects of dntgs identified was the troponin C of skeletal .. admuwcd to the motlur during peg- muscle, but it is now widely acceptedthat nancy on tbe infant, the potential of the the main cytoplasmic ‘Gas* receptor’ in bteastas a toute for drug excretion and sub other eukaryotccclis (whether plant or pm. sequenfeffectson the infant have been very tist. testicle or tumour) is Cahnodulin, a poorly studied. small protein that is highly conserveddurThe pharmacokinetic chapter gives a ing evolution, is acidic and binds four Caa’ basictt&seonthcpropertiesgovemingthe ions. tram&r of drugs across biological mem Is a broad faith in the functional versatiG bmnes and n&sting these to milk charac- ity of this widespreadproteinju~~~~ Are lbere other, as yet unidentified(or lesspub licixed). cytoplasmicCa” receptors?How good are the tools we use to investigatethe functions of calmodulin (and hence the answersthey yield)? How com%zt,and how generally a~~~b~, m our cuncnt mechanistic models of calmodulin’s actions?Ideally. a book entitledGdmodubt and Cell Funct~~ would directly addresssuch questtons,and it might even do so in languagethat would attract a sub stantial audiince fmm the many outsiders who now find themselvestrying to join the calmodulincommunity. This beok does not achieve that ideal, probably for two reasons:the field is too young for other thanprovisionalanswersto the questions above, and this volmne
For aficionados?
J 982
_I
some of the pharmacologically active agents discussed on infant hehaviour is extremely brief with a si~n~~c~t proportion of the results being derived,ftwm sub. primate animals. The diBlculties in obtain. ing data from humansis discussed. This is an extremely useful piece of work, praiseworthy for both the contentof the i~ivid~ ~t~butio~ and the extensive natureof the referencesit provides. LIDIA J. NOTARIANNI
records the proceedings of a meeting of convinced calmodulin aficionados who have mostly written for li*& felktw club members. rfowever, it will long remain a mine of information on all &pects of calrn~~in structuteand batiks. but a mine that will only yield its richesafter considerable toil by the reader. Amongst the most intriguingnugg&i arc a variety of hintsasto importantnew diitions that work on caimodulin is taking. Examples include: the impcctanceof interactionswith ~~iphilic molecules, be they inhibitory cationic drugs such as trifhrornperaxine (almost everyone’s un~liahie(?) test for calmodu. tin’s involvementin any cellular process) or anionic activatory notGonired or ~~i~i~~ (ted cell Ca*+-ATPase in anionic lipid liposomes respondsfully IO Cax’ even without calmoduhn!); a prob. able role for catmodulin in the @armacological adjustment of dopamine recep tar sensitivitvin v&o. and the localixxtion of calmodul~ (without es~~bJ~hedfunctions) on both sides of many synapses,so that new ideas for calmoduhn function in the CNS ate emerging at the same time as Weiss’s arguments that calmodulin is a major receptor for antipsychotic dntgs stem to be fading; the identification of at least two enzymes ( I S.hydmxyprostaglandindehydmgenase and cardiac adenylate cyclase) that show calmodulin dependent inhibition by Cal’; the wide spread involvement of cabnodulin in con trol of Gas’ transportat membranes,prob. ably by severaldifferent mechanisms. To summarize, this is a useful book bur one that is, becatuseof it.. style and its very Sigh price, destinedmainly for Muaries and experts. R. H. MICHELL