A History of Gastric Secretion and Digestion: Experimental Studies to 1975

426 Pages·1992·11.789 MB·English

by  Horace W. Davenport (auth.)

A History of Gastric Secretion and Digestion
A History
of Gastric Secretion
and Digestion
Experimental Studies to 1975
HORACE W. DAVENPORT
William Beaumont Professor of Physiology Emeritus
The University of Michigan
Springer New Y ork
1992
Copyright © 1992 by the American Physiological Society
Originally published by American Physiological Society in 1992
Softcoverreprint of the bardeover 1st edition 1992
All rights reserved. No partoftbis publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording, or otherwise,
without the prior permission ofOxford University Press.
Library ofCongress Cataloging-in-Publication Data
Davenport, Horace Willard, 1912-
A history of gastric secretion and digestion : experimental
studiesto 1975 I Horace W. Davenport.
p. cm. lncludes bibliographical references and index.
ISBN 978-1-4614-7602-3 (eBook)
DOI 10.1007/978-1-4614-7602-3
I. Gastroenterology-History.
2. Gastric-Secretion-Research-History.
3. Digestion-Research-History.
I. Title.
[DNLM: I. Digestion.
2. Gastric Acid-secretion.
3. Gastroenterology-history.
4. Research-history.
5. Stomach-chemistry.
6. Stomach-physiology.
Wlll.l D247h] QP145.D325 1992
612.3'2'072-dc20 DNLM/DLC
for Library ofCongress
91-31832
987654321
For Charles F. Code,
known to every gastroenterologist as "Charlie Code"
and as their preeminent physiologist for the last
fifty years
Preface
For centuries men speculated about the process of gastric digestion, but Iate in the
eighteenth and early in the nineteenth centuries physiologists, both physicians and
laymen, began to accumulate experimental evidence about its nature. At the same
time, others discovered that the stomach is capable of secreting a strong mineral
acid, and the questions of how that secretion is produced and how it is controlled
became enduring problems. A Iittle later, the discovery that an acid extract of dead
gastric mucosa is capable of digesting meat put the study of gastric secretion and
digestion on a firm mechanistic foundation. From that time to the present, physi
ologists have assiduously investigated gastric secretion and digestion, with the result
that knowledge ofthose topics is as comprehensive and penetrating as isthat about
other physiological processes. In addition, that knowledge is the basis of discrimi
nating and effective clinical practice.
I have described the experimental study of gastric secretion and digestion for
two reasons. The firstisthat the successes and some ofthe failures ofphysiologists
over two centuries are important parts of intellectual history that deserve to be
recorded. The second is that some of those who use the accumulated knowledge
every day are curious about its genesis. I assume that my readers have the technical
knowledge to understand what I have written. If my account does not fully satisfy
their curiosity, I have provided references that will open the path to further study.
This account is necessarily conditioned by my own knowledge, ability, and
enterprise, and those have their Iimits. Furthermore, I Iimit my account by begin
ning with the period 1777 to 1833 when the pioneers of experimental gastroenter
ology, Edward Stevens, William Beaumont, Johann Eberle, and their contempo
raries, began to gather experimental evidence. I end in 1975, the date of Charlie
Code's retirement from the Mayo Clinic and Mayo Foundation, for ifl attempted
to bring the account more nearly up-to-date, it would have degenerated into an
indigestible review of current work.
I have myself studied gastric physiology in the laboratory for more than 40
viii / PREFACE
years, and some readers may think I have unduly emphasized my own work. That
may be the case, and the limits of my own outlook may have prevented me from
giving appropriate weight to the work ofo thers. A far more restrictive limit has been
imposed by an attitude typical of one who has been a professor of physiology in an
American medical school all bis professionallife. I and my colleagues on medical
faculties assume, often unconsciously, that the proper aim of physiological research
is to reach an understanding of normal and abnormal function in the human being.
We may work at the molecular or subcellular level, or we may use the ubiquitous
medical student or patient as our experimental animal, but our goal is the same.
Consequently, when I write about the history ofthe physiology of gastric secretion
and digestion, I am writing about a very limited number of species, the human sub
ject and the dog, cat, and frog. I completely ignore ruminant physiology and the
large and diverse knowledge of the physiology of the stomach in other species,
invertebrate as well as vertebrate. I make no apology for the narrowness of my out
look, for I believe my potential readers share it.
Ann Arbor, Mich. H.W.D.
September 1991
Acknowledgments
My greatest debt is to the University of Michigan and to Jack Kostyo and John
Williams, my successors as chairmen ofthe department ofphysiology, for allowing
me the use of an office long past my retirement from the faculty. The university's
Taubman Medical Library and Hateher Graduate Library have been rieb
resources, and their reference librarians have been uniformly helpful. I am grateful
to the many gastroenterologists who made my task easier by sending me their bib
liographies and in particular to Paul Guth, who took the trouble to find a Iist of
Morton Grossman's numerous publications. Charlie Code gave me a copy ofhis
even moreimpressive bibliography and a guide to the work ofhis colleagues at the
Mayo Clinic. Code read my original typescript, and bis comments and corrections
improved it. I am, however, entirely responsible for errors, oversights, and misin
terpretations.
Contents
1 . Secretion of Hydrochloric Acid, 3
Site of Secretion, 3
Structure ofthe Oxyntic Cell, 4
Site of Appearance of Acid, 5
Concentration of Acid, 8
Free and Combined Acid in the Human Stomach, 8
In the Dog: Two Components, l3
The Problem ofTonicity, 18
An Alternative to Two Components: Back-Diffusion, 19
Secretion of Anions, 24
Bromide and Chloride, 24
Active Secretion ofChloride: Adrian Hogben, 27
Iodide, 29
Mechanism of Acid Secretion, 32
Carbonic Anhydrase in Parietal Cells, 33
Thiocyanate and Carbonic Anhydrase, 36
Carbonic Anhydrase and Sulfanilamide, 39
Digression on Sulfonamide Secretion into Gastric Juice, 41
Postwar Theories of the Mechanism, 46
The Redox Theory: E. J. Conway, 46
Acid Secretion by the Frog Stomach: Robert E. Davies, 47
ls the Ratio ofQuotients Greater Than 4?, 51
xii / CONTENTS
Electrophysiology ofSecretion: Warren S. Rehm, 56
Electrolyte Composition ofthe Gastric Mucosa, 59
Chloride Transport by Isolated Oxyntic Cells, 62
Asymmetry ofthe Gastric Mucosa, 64
Identification ofPotassium Fluxes, 67
Thiocyanate Again, 67
Potential Differences Caused by Ion Transport, 68
Energy for Acid Secretion, 69
The Canalicular Membrane, 71
SUMMARY Secretion of Hydrochiarie Acid as of 1975, 74
2. Pepsinsand Pepsinogens, 76
Chemistry of Pepsins to 1900, 76
Proteins: Their Names, 76
Characterization of Proteins, 77
Organic Components of Proteins, 78
Gastric Digestion ofProteins, 78
The Discovery of Pepsin, 80
Does Gastric Juice Merely Dissolve Proteins?, 81
ChiefCells and Their Contents, 82
Chemistry of Pepsin and lts Substrate, 84
The Peptide Bond, 84
Characteristics of Proteins: Their Individuality, 85
Characteristics of Proteins: Molecular Weight, 85
Characteristics of Proteins: Amino Acid Sequence, 85
Characteristics of Proteins: Configuration, 86
Pepsin as a Protein and a Proteolytic Enzyme, 87
Is Pepsin a Protein?, 87
Activity ofPepsin: Bonds Split, 89
Pepsinogen: Crystallization and Properties, 89
Pepsinogen in Urine and Blood, 89
Source ofUropepsin, 91
Clinical Studies ofSerum Pepsinogen and Uropepsin, 92
Uropepsin and Stress, 92
Multiple Pepsinsand Pepsinogens, 94
Questions About Pepsin, 94
S.Oren S.Orensen's Contribution, 94
Pepsin's pH Activity Curve, 95