The Transfer of Calcium and Strontium Across Biological Membranes

439 Pages·1963·10.496 MB·English

by  R. Wasserman (Eds.)

The Transfer of
Calcium and Strontium
Across Biological Membranes
Proceedings of a Conference held at Cornell University
Ithaca, New York, May 13-16, 1962
Edited by
R. H. WASSERMAN
Department of Physical Biology
New York State Veterinary College
Cornell University
Ithaca, New York
1963
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LIST OF PARTICIPANTS
ARMSTRONG, W. D., Department of Phys- CLARK, I., Department of Orthopedic
iological Chemistry, University of Surgery, Columbia University, Col-
Minnesota, Minneapolis, Minnesota lege of Physicians and Surgeons, New
ASDELL, S. A., Department of Animal York, New York
Husbandry, N. Y. S. College of Agri- COM AR, C. L., Department of Physical
culture, Cornell University, Ithaca, Biology, N. Y. State Veterinary Col-
New York lege, Cornell University, Ithaca, New
AVIOLI, L. V., Seton Hall College of York
Medicine and Dentistry, Medical CONNOR, T. B., Department of Medicine,
Center, Jersey City, New Jersey University of Maryland School of
BARNES, R. H., Graduate School of Nutri- Medicine, Baltimore, Maryland
tion, Cornell University, Ithaca, New COPP, D. H., Department of Physiology,
York University of British Columbia, Van-
BERGER, E. Y., Research Service, Third couver, B.C., Canada
N. Y. U. Medical Division, Goldwater COUSINS, B., Department of Radiation
Memorial Hospital, New York, New Biology, University of Rochester,
York Rochester, New York
BERGMAN, E. N., Department of Phys- CRAMER, CF., Department of Physiology,
iology, N. Y. S. Veterinary College, University of British Columbia, Van-
Cornell University, Ithaca, New York couver, B.C., Canada
BERGSTROM, W. H., Pédiatrie Department, CURRAN, P. F., Biophysical Laboratory,
S. U. N. Y. Medical Center, Syracuse, Harvard Medical School, Boston, Mas-
New York sachusetts
BERNSTEIN, D., Division of Medicine, DANIEL, L. J., Department of Biochemis-
Mount Sinai Hospital, Los Angeles, try, Cornell University, Ithaca, New
California York
BORLE, A. B., Department of Radiation DAVIS, A. K., Radiological Health Labora-
Biology, University of Rochester, tory, Department of Health, Educa-
Rochester, New York tion, and Welfare, Public Health
BREEN, M., Northwestern University Service, Rockville, Maryland
Medical School, Chicago, Illinois DAVIS, G. K., Nuclear Sciences, Nutrition
BRONNER, F., Hospital for Special Surgery, Laboratory, University of Florida,
Cornell University Medical Center, Gainesville, Florida
New York, New York DELLA ROSA, R. J., School of Veterinary
BUDY, A. M., Department of Physiology, Medicine, University of California,
University of Chicago, Chicago, Davis, California
Illinois DOB SON, A., Department of Physiology,
BREUER, L. H., Department of Animal N. Y. State Veterinary College, Cor-
Husbandry, Cornell University, Ith- nell University, Ithaca, New York
aca, New York DRAPER, H. H., Animal Sciences Labora-
CHEN, P. S., Department of Radiation tory, University of Illinois, Urbana,
Biology, University of Rochester, Illinois
Rochester, New York DUPUIS, Y., Centre National Recherche
CHOWDHURY, T. K., Department of Bio- Scientifique, Laboratoire du Physi-
physics, University of Buffalo, Buf- olgie de la Nutrition, Paris, France
falo, New York EGAWA, J., Department of Radiation Biol-
V
VI LIST OF PARTICIPANTS
ogy, University of Rochester, Roch- HEANEY, R. P., School of Medicine,
ester, New York Creighton University, Omaha, Ne-
FILONOWICH, L. K., Department of Phys- braska
iological Chemistry, University of HENDRIX, J. Z., Endocrinology Depart-
Minnesota, Minneapolis, Minnesota ment, Rockefeller Institute, New
FOWLER, E. B., University of California, York, New York
Los Alamos, New Mexico HENNEMAN, P. H., Seton Hall College of
FRASER, D., The Research Institute, Hos- Medicine, Jersey City Medical Center,
pital for Sick Children, Toronto, Jersey City, New Jersey
Ontario, Canada HOGBEN, C. A. M., Department of Phys-
FRIES, G. F., Department of Physical Biol- iology, State University of Iowa, Iowa
ogy, Cornell University, Ithaca, New City, Iowa
York, and U. S. Department of HOLLAND, R. F., Department of Dairy and
Agriculture Food Science, Cornell University, Ith-
FUERST, W. F., Department of Physiology, aca, New York
N. Y. State Veterinary College, Cor- HUBEL, K. A., 9001 Louis Avenue, Silver
nell University, Ithaca, New York Spring, Maryland
GARLICH, J. D., Poultry Department, Cor- HUNT, B. J., Department of Medicine,
nell University, Ithaca, New York University of Toronto, Toronto, On-
GASTEIGER, E. L., Department of Physical tario, Canada
Biology, N. Y. S. Veterinary College, ICHIKAWA, S., Department of Physical
Cornell University, Ithaca, New York Biology, N. Y. S. Veterinary College,
GIESE, W., Department of Physical Biol- Cornell University, Ithaca, New York
ogy* N. Y. S. Veterinary College, JAINUDEEN, M. R., Department of Animal
Cornell University; and Hannover, Husbandry, Cornell University, Ith-
Germany aca, New York
GRAY, L. F., U. S. Nutrition Laboratory, JAYASINGHE, J. B., Ceylon
Cornell University, Ithaca, New York JOHNSON, R. F., Marine Laboratory, Uni-
GREENFIELD, L. J., Marine Laboratory, versity of Miami, Florida
University of Miami, Florida JOHNSTON, F. A., Department of Food and
HACKLER, L. R., Department of Food Nutrition, N. Y. S. College of Home
Science, Cornell University, Geneva, Economics, Cornell University, Ith-
New York aca, New York
HANSEL, W., Department of Animal KIRSCHNER, L. B., Department of Zoology,
Husbandry, Cornell University, Ith- Washington State University, Pull-
aca, New York man, Washington
HARDY, E., U. S. Atomic Energy Com- KODICEK, E., Dunn Nutritional Laboratory,
mission, Health and Safety Labora- University of Cambridge and Medical
tory, New York, New York Research Council, Cambridge, Eng-
HARKINS, R. W., Mead Johnson Research land
Center, Evansville, Indiana KOPRIVA, P. C, State University of New
HARRISON, G. E., Radiobiological Research York, New Paltz, New York
Unit, Medical Research Council, Har-
KOSIKOWSKI, F., Department of Dairy and
well, England
Food Science, Cornell University, Ith-
HARRISON, H. E., Pediatrics Department,
aca, New York
Johns Hopkins University, Baltimore,
Maryland LAGUE, JEAN-GUY, Faculty of Dentistry,
HAY, P., Strong Memorial Hospital, Uni- University of Montreal, Montreal,
versity of Rochester, Rochester, New Quebec, Canada
York LAZOR, M. Z., National Cancer Institute,
LIST OF PARTICIPANTS vii
National Institutes of Health, Be- Medicinsk — Kemiska Institutionen,
thesda, Maryland Medicinaregaten 9, Göteborg, Sweden
LEDFORD, R. A., N. Y. State Department MIGICOVSKY, B. B., Biochemical Research
of Agriculture and Markets, Albany, Branch, Canada Department of Ag-
New York riculture, Ottawa, Ontario, Canada
LENGEMANN, F. W., Department of MILLER, E. J., Radiation Biology Depart-
Physical Biology, N. Y. S. Veterinary ment of the School of Dentistry and
College, Cornell University, Ithaca, Medicine, University of Rochester,
New York Rochester, New York
LINDQUIST, B., University of Umea Medi- MILLICAN, C, N. Y. State Department of
cal School, Umea, Sweden Health, Rochester, New York
LOOSLI, J. K., Department of Animal MONROE, R. A., Research and Develop-
Husbandry, Cornell University, Ith- ment Division, National Dairy Prod-
aca, New York ucts Corporation, Glenview, Illinois
LUTWAK, L., Metabolic Diseases Branch, MOORE, W., Southeastern Radiological
National Institute of Arthritis and Health Laboratory, Public Health
Metabolic Diseases, National Institutes Service, Montgomery, Alabama
of Health, Bethesda, Maryland MORI, K., Institut de Gerontologie, Hôpital
LYON, L, Department of Biochemistry, Nôtre Dame de la Merci, Montreal,
Chicago Medical School, Chicago, Quebec, Canada
Illinois MORRISON, M., Department of Food and
MCFARLAND, W., Department of Zoology, Nutrition, Cornell University, Ithaca,
Cornell University, Ithaca, New York New York
MCLEAN, F. C, Department of Physiology, MULRYAN, B., University of Rochester
University of Chicago, Chicago, Medical Center, Rochester, New York
Illinois NESHEIM, M. C, Poultry Department,
MALETSKOS, C. J., Physics Department, Cornell University, Ithaca, New York
Massachusetts Institute of Tech- NEUMAN, W. F., Department of Radiation
nology, Cambridge, Massachusetts Biology, University of Rochester,
MALM, O. J., Institute for Experimental Rochester, New York
Medical Research, Ullevaal Hospital, NEWTON, C. F., Medical Department,
Oslo, Norway University of Chicago, Chicago,
MARCUS, C. S., Department of Physical Illinois
Biology, N. Y. S. Veterinary College, NICHOLS, B., Electrical Engineering, Cor-
Cornell University, Ithaca, New York nell University, Ithaca, New York
MASUHARA, T., Animal Research Institute, NICHOLS, G., Harvard Medical School,
Canada Department of Agriculture, Boston, Massachusetts
Ottawa, Ontario, Canada NICOLAYSEN, R., Institute for Nutrition
MASUROVSKY, E. B., Department of Food Research, University of Oslo, Blind-
Science and Technology, Nutrition, em, Norway
NORDIN, B. E. C, Medicine Department
Massachusetts Institute of Tech-
of Gardiner Institute, Western In-
nology, Cambridge, Massachusetts
firmary, Glasgow, Scodand
MAURICE, P. F., Seton Hall College of
OTERO, L. R., Department of Zoology,
Medicine, Jersey City Medical Center,
Columbia University, New York,
Jersey City, New Jersey
New York
MAYNARD, L. A., Department of Bio- PACHA, F., Animal Research Institute, Re-
chemistry and Nutrition, Cornell Uni- search Branch, Central Experimental
versity, Ithaca, New York Farm, Canada Department of Agri-
MELLANDER, O., Göteborgs Universitet, culture, Ottawa, Ontario, Canada
Vlll LIST OF PARTICIPANTS
PEACHEY, L. D., Department of Zoology, Biology, N. Y. S. Veterinary College,
Columbia University, New York, Cornell University, Ithaca, New
New York York; and Harwell, England
PEREZ, C. B., Department of Animal SAX, N. I., Radiological Sciences Group,
Husbandry, Cornell University, Ith- Division of Laboratories and Re-
aca, New York search, N. Y. State Department of
PETERS, L. H., University of Oregon Health, Albany, New York
Dental School, Pordand, Oregon SCHACHTER, D., Columbia University Col-
PRITHAM, G. H., Frear Laboratory, lege of Physicans and Surgeons,
Department of Agriculture and Bio- Presbyterian Hospital, New York,
chemistry, Penn State University, New York
University Park, Pennsylvania SCHRAER, H., Biophysics Laboratory,
RAISZ, L. G., Department of Pharmacol- Physics Department, Penn State Uni-
ogy, University of Rochester, Roch- versity, University Park, Pennsylvania
ester, New York SCHWARTZ, R., Western Reserve Univer-
RAY, R. D., Department of Orthopedic sity, Cleveland, Ohio
Surgery, University of Illinois College SHANES, A. M.,* Department of Phar-
of Medicine, Chicago, Illinois macology, Schools of Medicine, Uni-
READ, M. S., National Dairy Council, versity of Pennsylvania, Philadelphia,
Chicago, Illinois Pennsylvania
REEVES, R. B., Department of Zoology, SINGER, L., Physiological Chemistry De-
Cornell University, Ithaca, New York partment of the Medical School,
RIVERA, J., U. S. Atomic Energy Com- University of Minnesota, Minneapolis,
mission, Health and Safety Labora- Minnesota
tory, New York, New York SNELL, F. M., Department of Biophysics,
ROBINSON, B. H. B., Pharmacology and University of Buffalo, Buffalo, New
Experimental Therapeutics Depart- York
ment, Johns Hopkins University, SOLOMON, A. K., Biophysics Laboratory,
Baltimore, Maryland Harvard Medical School, Boston
ROE, W. E., Department of Veterinary Massachusetts
Physiology, N. Y. S. Veterinary Col- SPERELAKIS, N., Physiology Department,
lege, Cornell University, Ithaca, New Western Reserve University, Cleve-
York land, Ohio
RUBIN, M., Chemo-Medical Research In- STEIN, I., Orthopedic Department, Albert
stitute, Graduate Chemistry Depart- Einstein Medical Center, Philadel-
ment, Georgetown University Medical phia, Pennsylvania
School, Washington, D.C. STEVENS, C. E., Department of Veterinary
ROSENTHAL, H. L., Washington Univer- Physiology, N. Y. S. Veterinary Col-
sity, St. Louis, Missouri lege, Cornell University, Ithaca, New
York
S ABÊTI RAHMATI, H., Department of
Physical Biology, N. Y. S. Veterinary TALMAGE, R. V., Biology Department,
College, Cornell University, Ithaca, Rice University, Houston, Texas
New York TAVES, D., Department of Radiation Biol-
SALTMAN, P., Department of Biochemistry ogy, University of Rochester, Roch-
and Nutrition, University of South- ester, New York
ern California School of Medicine, TELLES, N. C, New England Deaconess
Los Angeles, California Hospital, Boston, Massachusetts
SAMACHSON, J., Veterans Administration TEREE, T., University Hospitals, Cleve-
Hospital, Hines, Illinois land, Ohio
SAVAGE, J. R. K., Department of Physical THOMAS, W. C, Department of Medicine,
* Deceased
LIST OF PARTICIPANTS IX
University of Florida College of Med- WELLMAN, H. N., Division of Radio-
icine, Gainesville, Florida logical Health, Robert A. Taft Sani-
THOMPSON, R. C, General Electric Com- tary Engineering Center, Cincinnati,
pany, Hanford Atomic Products Op- Ohio
eration, Richland, Washington WHEDON, G. D., Metabolic Diseases
TIDBALL, C. S., Physiology Department, Branch, National Institute of Ar-
George Washington University, thritis, and Metabolic Diseases, Na-
tional Institutes of Health, Bethesda,
Washington, D.C.
Maryland
TOVERUD, S. U., Institute for Nutrition
Research, University of Oslo, Blind- WIDDOWSON, E. M., Department of Ex-
perimental Medicine, Medical Re-
em, Norway
search Council, Cambridge, England
TWARDOCK, A. R., Department of Physical
WILLIAMS, G. A., Radioisotope Service,
Biology, N. Y. S. Veterinary College,
Veterans Administration, Westside
Cornell University, Ithaca, New York
Hospital, Chicago, Illinois
URIST, M. R., Department of Surgery,
WILSON, D. R., Department of Medicine,
University of California Medical
University of Toronto, Toronto, On-
Center, Los Angeles, California
tario, Canada
VAUGHAN, O. W., ROSS Laboratories,
WOODARD, H. Q., Sloan — Kettering In-
Columbus, Ohio
stitute, New York, New York
WALSER, M., Department of Pharmacol-
WOOLLEY, D. W., Rockefeller Institute,
ogy and Experimental Therapeutics, New York, New York
Johns Hopkins University, Baltimore, WRIGHT, L. D., Graduate School of Nutri-
Maryland tion, Cornell University, Ithaca, New
WASSERMAN, R. H., Department of York
Physical Biology, N. Y. S. Veterinary YENDT, E. R., Department of Medicine,
College, Cornell University, Ithaca, University of Toronto, Toronto, On-
New York tario, Canada
WAUGH, W. H., Department of Medicine, YOUNG, C. M., Graduate School of Nutri-
University of Kentucky College of tion, Cornell University, Ithaca, New
Medicine, Lexington, Kentucky York
WEIL, W. B., University Hospitals of YOUNG, R. J., Poultry Department, Cornell
Cleveland, Cleveland, Ohio University, Ithaca, New York
PREFACE
The present volume represents the proceedings of a Conference held at
Cornell University, Ithaca, New York, May 13-16, 1962. The Conference,
being of the same name as the title of this book, was organized upon the
recommendation of a number of experts in the field. It was felt that there
was enough new information and concepts becoming available to warrant a
gathering of investigators for purposes of discussion and exchange of in-
formation. With the kind support of the U. S. Atomic Energy Commission,
the National Institute of Dental Research, the National Science Foundation
and Cornell University, such a meeting was made possible.
Calcium, of course, is an essential cation necessary for the functioning of
several enzyme systems, for blood clotting, for normal nerve and muscle
function, for bone formation and for maintaining the integrity of biological
membranes. Its concentration in blood and other body fluids is closely con-
trolled primarily by the action of the parathyroid glands. Strontium, not
known to have any biological function, is of interest because of its presence in
fissionable material and, for this volume, because of its similarity (chemical,
physical and biological) to calcium. Considerable time and effort has (and
is) being given to the problem of how calcium functions in these several
systems. Perhaps related to this and of equal importance, is the question of
how calcium moves across cells and cellular membranes. One may ask, for
example, what types of transfer processes are involved and which pre-
dominates under normal physiological and nutritional situations? In reference
to intestinal absorption, what mechanisms are available for altering the
degree of calcium transfer in response to varying calcium intakes. How does
vitamin D exert its effect? And what of the other factors, such as lactose, that
also influence these processes? Is calcium reabsorbed from the kidney tubule
by the same mechanism that operates in the intestine?
The problems concerning radiostrontium (Sr89 and Sr90) are perhaps
somewhat different but just as significant. After these radionuclides have
been absorbed and deposited in bone, only a small amount can be re-
moved except by exceedingly drastic measures. A more promising approach
would be to prevent or depress their intestinal absorption as quickly and as
efficiently as feasible. In order to attack this problem intelligently, one
should know by what process or processes strontium is actually absorbed.
It was to such problems and questions as alluded to above that the theme
of this volume (and the Conference) was addressed. Certainly, all of the
answers are not yet available and many of the solutions are still many years
away. It is hoped that this undertaking will serve to shorten, if only briefly,
the lag time.
xi
Xll PREFACE
With gratitude, the fine cooperation of the program committee, consisting
of Dr. R. H. Barnes (Cornell University), Dr. C. L. Comar (Cornell Uni-
versity), Dr. D. H. Copp (University of British Columbia), and Dr. H. E.
Harrison (Johns Hopkins University) is acknowledged. Sincere appreciation
is extended to the session chairmen who also served as sectional editors,
these being: (I) Dr. A. K. Solomon and Dr. P. F. Curran (Harvard Uni-
versity), (II) Dr. B. B. Migicc/sky (Canada Department of Agriculture,
Ottawa), (III) Dr. R. Nicolaysen (University of Oslo, Norway), (IV) Dr.
Bertil Lindquisf (University of Umea, Sweden), (V) Dr. Felix: Bronner
(Hospital for Special Surgery, Cornell Medical Center), (VI) Dr. F. C.
McLean ^University of Chicago), (VII) Dr. D. H. Copp (University of
British Columbia). Many others, particularly Howard Spicer, Jennifer Whel-
don, Ruth Ditzell and Eleanor Rosica, were most helpful in the organization
of the Conference and in the preparation of the discussion for the publisher.
The suggestions and advice of Dr. C. L. Comar proved most valuable and
his contributions are acknowledged with many thanks.
Ithaca, New York R. H. WASSERMAN
October, 1963
INTRODUCTORY COMMENTS
Rapid progress in the gaining of fundamental knowledge is bound to
result from a happy convergence of men with ideas and motivation, an
opportunity for personal communication, a highly developed state of the
art, and availability of material capabilities. The men with ideas are well
represented here as contributors to this conference on calcium and stron-
tium transport. The conference itself provides the market-place for ideas
where sparks are expected from the clash of minds. Over the years there
has been a sustained research interest in the nutritional and physiological
aspects of calcium metabolism. Nevertheless, it is fair to state that the
problems posed by the advent of atomic energy on a large scale provided
considerable motivation and stimulation that led to intensification of studies
of both calcium and strontium. Ironically, but perhaps with a measure of
poetic justice, the same developments that brought the issue into being
have also provided specific experimental tools and material capabilities that
have furthered the solution of these problems as well as of many others.
Since the very early experiments, it has been generally accepted that cal-
cium and strontium are interrelated in metabolic behavior. This means first
of all that possible effects of radioactive strontium should be looked for in
relation to those functions known to be dependent upon calcium:—skeletal
processes, coagulation of blood, contractility of muscle, reactivity of the
nervous system, and linkage in the nucleus of the cell. There is still a mild
controversy about whether the behavior of adventitious radiostrontium in the
mammalian organism is governed by the levels of stable strontium or by the
homeostatic action of calcium plus strontium. Though many incline to the
latter view, numerous observations yet remain to be explained. Hopefully,
clarification will be provided by an understanding of the details of transport
(e.g. competition, if any, for binding sites; carriers; energy sources). This
conference, not entirely by chance, comes at a time when research in the
broad area of mineral metabolism is about to take another tack. We know
reasonably well what happens in the body under certain conditions to
minerals such as calcium and strontium. Now we require to know why it
happens and how we can change the pattern of events at will.
When the strontium problem first blossomed, it was optimistically
thought that all the necessary information was existent in the voluminous
literature on calcium:—ready for the taking. But the welter of conflicting
views on even the most mundane aspects of calcium metabolism was dis-
illusioning. It appeared that, if generalizations were to be possible, there
must be much more basic information provided to shore-up the innumerable
ad hoc findings.
Xlll