Table Of ContentKININS IV 
Part A
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 
Editorial Board: 
NATHAN BACK, State University of New York at Buffalo 
NICHOLAS R. DI LUZIO, Tulane University School of Medicine 
EPHRAIM KATCHALSKI-KATZIR, The Weizmann Institute of Science 
DAVID KRITCHEVSKY, Wistar Institute 
ABEL LAJTHA, Rockland Research Institute 
RODOLFO PAOLETTI, University of Milan 
Recent Volumes in this Series 
Volume 192 
MECHANISMS OF STIMULUS-RESPONSE COUPLING IN PLATELETS 
Edited by J. Westwick, M. F. Scully, D. E. MacIntyre, and V. V. Kakkar 
Volume 193 
METHODS IN PORPHYRIN PHOTOSENSITIZATION 
Edited by David Kessel 
Volume 194 
MYOCARDIAL AND SKELETAL MUSCLE BIOENERGETICS 
Edited by Nachman Brautbar 
Volume 195A 
PURINE AND PYRIMIDINE METABOLISM IN MAN V, Part A: Clinical Aspects 
Including Molecular Genetics 
Edited by W. L. Nyhan, L. F. Thompson, and R. W. E. Watts 
Volume 195B 
PURINE AND PYRIMIDINE METABOLISM IN MAN V, Part B: Basic Science Aspects 
Edited by W. L. Nyhan, L. F. Thompson, and R. W. E. Watts 
Volume 196 
STEROID HORMONE RESISTANCE: Mechanisms and Clinical Aspects 
Edited by George P. Chrousos, D. Lynn Loriaux, and Mortimer B. Lipsett 
Volume 197 
BIOLOGICAL REACTIVE INTERMEDIATES III: Mechanisms of Action in 
Animal Models and Human Disease 
Edited by James J. Kocsis, David J. Jollow, Charlotte M. Witmer, 
Judd O. Nelson, and Robert Snyder 
Volume 198A 
KIN INS IV, Part A 
Edited by Lowell M. Greenbaum and Harry S. Margolius 
Volume 198B 
KININS IV, Part B 
Edited by Lowell M. Greenbaum and Harry S. Margolius 
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KININS IV 
Part A 
Editedhy 
Lowell M. Greenbaum 
Medical College of Georgia 
Augusta, Georgia 
and 
Harry S. Margolius 
Medical University of South Carolina 
Charleston, South Carolina 
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data 
International Kinin Congress (4th: 1984: Savannah, Ga.) 
Kinins IV. 
(Advances in experimental medicine and biology; v. 198) 
"Proceedings of the Fourth International Kinin Congress,  held October 21-25, 1984, in 
Savannah, Georgia" - T.p. verso. 
Includes bibliographies and index. 
1.  Kinins-Congresses.  2.  Kallikrein-Congresses.  I.  Greenbaum,  Lowell  M.  II. 
Margolius,  Harry S.  III.  Title.  IV.  Title:  Kinins 4.  V.  Series.  [DNLM:  1.  Kinins 
congresses. WI AD559 v.198/QU 68 1593 1984k] 
QP552.K5154  1984  599/.019/24  86-9403 
ISBN-13: 978-1-4684-5145-0  e-ISBN-13: 978-1-4684-5143-6 
DOl: 10.1007/978-1-4684-5143-6 
Proceedings of the Fourth International Kinin Congress, 
held October 21-25, 1984, in Savannah, Georgia 
© 1986 Plenum Press, New York 
Softcover reprint of the hardcover 1s t edition 1986 
A Division of Plenum Publishing Corporation 
233 Spring Street, New York, N.Y. 10013 
All rights reserved 
No part of this book may be reproduced, stored in a retrieval system, or transmitted 
in any form or by any means, electronic, mechanical, photocopying, microfilming, 
recording, or otherwise, without written permission from the Publisher
PREFACE 
Scientists from  25  countries  came  together at  the Hyatt  Regency 
Hotel  on October 21-25,  1984,  for  the  4th  International Kinin Congress 
in the beautiful city of Savannah,  Georgia.  Many  of  the  delegates 
enjoyed  southern hospitality for  the  first  time.  The  friendly city with 
its streets lined with  the Live Oak  Tree  (symbol  of  the Congress),  the 
balmy weather,  and  the excellent  facilities of  the hotel  set the  stage 
for  scientific events and exchange  that proved  so  successful.  The  organ 
ization of  the meeting was  the  result of many  hours,  days  and weeks  of 
effort by many,  including from Augusta  Drs.  James  H.  Sutherland,  John 
Catravas,  William Davis,  Jr.,  and Hiroshi Okamoto;  and  from  Charleston, 
SC,  Julie Chao,  Ronald Mayfield and Donald Miller.  Special  thanks  go 
to Ms.  Cher  Cornett of  the Department  of Medical  Illustration at  the 
Medical  College of Georgia  for her  talent  in the design of  the  logo,  as 
well  as  the  graphics of  the program and abstracts.  We  are  indeed 
indebted  to Dr.  Paul  Brucker,  Director of  the Division of Health Communi 
cations at  the Medical  College  of Georgia,  for his considerable aid in 
spending  time with us  to arrange  the programming  format  and  continuity. 
Ms.  Sandra Usry  provided very excellent and  devoted  secretarial help  for 
several years while  the Congress was  in  the making.  Thanks  also  to  the 
secretarial staff of  the Department  of  Pharmacology at MCG,  including 
Rosiland Simmons  and Jennie Doby  for  their expert assistance  during  the 
meeting.  We  also wish  to  thank the many  sponsors  (NIH,  Johnson & 
Johnson,  Bayer AG  and Bayer AG/Miles,  KabiVitrum AB,  American Heart 
Association,  Medical  College  of Georgia  Research Institute,  Rich's 
Travel,  Bayer Yakhuin,  Ltd.,  Bristol-Myers Co.,  Drug  Science Foundation 
of S.C.,  Sanwa  Kagaku  Ltd.,  Upjohn  Co.,  Hoffmann-La  Roche,  Inc., 
Boehringer  Ingelheim,  Ltd.,  Burroughs Wellcome  Co.,  Ciba  Geigy Pharma 
ceutical,  E.  R.  Squibb & Sons,  Inc.,  Fujimoto Pharmaceutical  Co.,  Ltd., 
Am.  Cyanamid Co.,  G.  D.  Searle,  E.  I.  DuPont  de  Nemours  & Co.). 
During  the early planning of  the Congress,  we  learned of  the  death 
of one  of  the world's great pharmacologists and discoverer of brady 
kinin,  Professor Mauricio Rocha  e  Silva of  Brazil.  Professor Rocha  e 
Silva not  only coined the name  for bradykinin but was  a  staunch advocate 
in his  own  special way  for  research allover the world  to  elucidate the 
importance of kin ins  and kallikreins in health and  in disease.  It is 
more  than  fitting that  the  4th  International Congress  of Kinins was 
dedicated to his memory  and efforts.  We  were most  fortunate  that his 
collaborator in the  discovery of bradykinin and a  great  scientist in his 
own  right,  Dr.  Wilson Beraldo  of Belo Horizonte,  attended the  Congress. 
All  of us were moved  by his sincere  tribute,  as well  as  the  tribute of 
Dr.  Mauricio Rocha  e  Silva,  Jr.,  to  Professor Rocha  e  Silva's contribu 
tions  to  science and  society.  Since  the close of  the  Congress we 
learned of  the deaths  of  three pioneers  in kinin research,  Dr.  John 
Pisano  (suddenly)  of  the NIH,  Dr.  Ulla Hamburg  of Finland and Dr.  Marion 
Webster,  formerly of  the NIH.  Each  of  these have  left  lasting impres-
v
sions on  us  because  of  their pioneering contributions,  their strength 
of purpose  in kinin  research  and  their love  of  aiding others  in our 
discipline.  We  will miss  them.  We  are privileged that  these volumes 
contain the  last scientific communications  of Drs.  Pisano  and Hamburg. 
"Kinin  '84 Savannah" had  a  number  of  "firsts".  It was  the  first 
Kinin Congress  to  encompass  four  full  days.  It was  the  first Congress 
to  institute "Frontier Lecturers" which provided us  with  information 
about  areas  of  research which may  be  vital  to  our growth  but with which 
we  may  not  be  familiar  at  this  time.  We  are all  indebted to  the  superb 
lecturers which  included Dr.  Hans  Fritz  (FRG),  Dr.  Robert  Colman  (USA), 
Dr.  S.  Nakanishi  (Japan),  Dr.  John  Shine  (Australia),  Dr.  Allen Cuthbert 
(England)  and Dr.  T.  Hokfelt  (Sweden).  This was  the  first Congress  to 
utilize the  concept  of  formal  "Poster Discussions"  so  that all  investi 
gators had a  chance  to  comment  on  their efforts  in addition  to  the  200 
posters  on  display.  We  are  indebted  to  the  discussion  leaders who  made 
the  14  sessions  so meaningful.  It was  the  first  of  the Kinin Congresses 
to  have  "competing" oral  sessions  and we  wish  to  thank  the  Chairman  and 
Co-chairman of  these  sessions,  as well  as  the  delegates  themselves,  for 
the  excellence of  the  80 oral  presentations.  This was  the  first  inter 
national meeting at which  the  T-kinin - T-kininogen  sysem was  intro 
duced,  as  well  as  several  components  of  the kallikrein-kinin system in 
brain  including kinins and kininases.  The  long  sought-after antagonist 
to  bradykinin as  well  as  the  isolation and  characterization of  the  genes 
expressing kininogen  synthesis was  described.  It was  the  first of  our 
meetings  to pay  tribute  to  our  pioneers  in kinin  research and we  again 
salute the  recipients,  Drs.  Melville  Schachter  (Canada),  Ervin Erdos 
(USA),  Wilson Beraldo  (Brazil),  Hector Croxatto  (Chile),  Tomoji  Suzuki 
(Japan),  and Gert  Haberland  (FRG).  It was  the  first meeting at which 
six young  investigators  from  five  countries were nominated as  KabiVitrum 
Scholars  and given  special  travel awards. 
Our  social  times  together also  left some  unforgettable memories. 
All  of  us  will  remember  the warm  friendship  and  the  beauty of  the 
evening and as  we  glided down  the Savannah  River on  the  riverboat  to 
shuck oysters  under  the  torchlight  and  accompanied  by  the  southern  jazz 
music  of  Fort Jackson.  We  were  truly a  "Kinin Family."  The  satellite 
meeting  in Hilton Head  and  the visitations  to  Charleston and Augusta 
provided additional  opportunities  for  interactions and  friendships. 
The  4th  International Kinin Congress was  a  stimulating experience 
for  us  and we  hope  the pages  of  these volumes  will keep  the  spirit and 
science  of Kinin  '84 Savannah alive for many  years  to  come. 
Lowell H.  Greenbaum,  Ph.D 
President,  IKC 
Augusta,  Georgia 
Harry S.  Margolius,  Ph.D,  H.D. 
Vice President,  IKC 
Charleston,  South Carolina 
vi
CONTENTS  - PART  A 
TISSUE  KININOGENASES 
The  Varied Localization and Functional  Significance of 
Kallikrein-Like Enzymes  in Salivary Glands,  Pancreas, 
Colon,  Sex Glands  and Spermatozoa,  Including 
Evidence  for the  Presence of Nerve  Growth 
Factor  (NGF)  in Bull  Sperm Acrosome..........................  I 
M.  Schachter,  M.W.  Peret,  The  Late C.  Moriwaki, 
G.D.  Wheeler,  R.W.  Matthews,  J.G.  Mehta 
and T.  Labedz 
Kininogenase  from  Rat  Vascular Tissue..............................  11 
H.  Nolly,  A.G.  Scicli, G.  Scicli, M.C.  Lama, 
A.M.  Guercio and  O.A.  Carretero 
Intracellular and  Intercellular Distributions of Acid 
Kininogenases  in Spleen......................................  19 
M.  Watanabe  and K.  Yamafuji 
Localization of Kallikreins  in the Human  Parotid and 
Gland  in the Human  Kidney:  A Comparative 
Study of  Immunohistochemistry and Enzyme 
Histochemistry...............................................  27 
K.  Kimura  and H.  Moriya 
Studies on  Carbohydrate  Structure and  Immunological 
Properties of Human  Urinary Kallikreins......................  35 
H.  Moriya,  M.  Ikekita and K.  Kizuki 
Initial Observations of a  Kallikrein-Like Enzyme 
Associated with the  Plasma Membranes  of 
Rat  Adipocytes...............................................  41 
F.  Mulholland,  A.  Ashford and G.S.  Bailey 
Bile Acids  and  the  Intestinal Kallikrein-Kinin 
System.......................................................  47 
I.J.  Zeitlin,  H.A.R.  AI-Dhahir,  S.  Cook, 
A.  Currie and K.  Donovan 
KININOGENS 
T-Kinin and T-Kininogen - An  Historical Overview...................  55 
L.M.  Greenbaum
Increased Plasma Level  of T-Kininogen in Rats 
Treated with Freund  s  Adjuvant...............................  61 
I 
A.  Barlas,  H.  Okamoto  and L.M.  Greenbaum 
Isolation and Properties of Two  Rat  Plasma 
T-Kininogens. . • • • . . . . • • • • • • • • • • • • • . • . • • • • • . • . • • • • • • • • • • • • • • • •  69 
H.  Okamoto  and L.M.  Greenbaum 
Characterization of Kininogen Deficiency of Brown 
Norway  Rat Mutant  Katholiek Strain...........................  77 
S.  Oh-ishi,  I. Hayashi,  T.  Ino,  H.  Kato, 
S.  Iwanaga and T.  Nakano 
Amino  Acid Sequence of the Light  Chain of Human  Low 
Molecular Mass  Kininogen.....................................  91 
F.  Lottspeich,  J.  Kellermann,  A.  Henschen, 
G.  Rauth and W.  Muller-Esterl 
Limited Proteolysis of HMW  Kininogen by  Plasma 
Kallikrein in Man- Evidence  for  a  Processing 
Mechanism Different  from  the  Bovine  System...................  97 
W.  Muller-Esterl,  H.  Hock,  G.  Rauth, 
J.  Kellermann,  F.  Lottspeich,  and A.  Henschen 
Interaction of Human  Low  Molecular Weight  Kininogen 
with Human  Mast  Cell Tryptase................................  105 
L.B.  Schwartz,  M.  Maier and J.  Spragg 
Independent Consumption of High and Low  Holecular Weight 
Kininogens  In Vivo...........................................  113 
Y.  Uchida and M.  Katori 
Urinary Kininogen:  A Possible Regulator of Kinin Formation 
in Normal  Individuals and Subjects with Essential 
Hypertension,  End-Stage Renal and Liver Disease..............  119 
M.S.  Weinberg,  U.M.  Trebbin,  and R.J.  Solomon 
Monoclonal  Antibodies  to Rat  Plasma  Kininogen......................  127 
G.S.  Bedi  and N.  Back 
Hydrolysis  of Rat  High Molecular Weight  Kininogen by 
Purified Rat  Urinary Kallikrein:  Identification 
of Bradykinin as  the Kinin Formed............................  137 
J.P.  Girolami,  F.  Alhenc-Gelas,  M.L.  Dos  Reis, 
J.L.  Bascands,  J.M.  Suc,  P.  Corvol.  and J. Menard 
Reduced  or Unchanged Cofactor Function of Human  High 
Molecular Weight  Kininogen  Induced by  Human 
Plasma  Kallikrein............................................  147 
H.T.  Johansen and K.  Briseid 
Studies on  the Antigenic Determinants of Human  Low 
Molecular Weight  Kininogen...................................  155 
T.  Karkkainen,  A.-C.  Syvanen and U.  Hamberg 
Kininogen by  the  SRI  Method  in Human  Serum During 
an Acute  Phase  Inflammatory Reaction.........................  161 
U.  Hamberg,  T.  Karkkainen  and T.  Tallberg 
Kininogen  as a  Pregnancy-Associated Plasma  Protein.................  167 
T.  Karkkainen and U.  Hamberg 
viii
Hemodynamics  of the Isolated Perfused Rat  Kidney 
in the Absence and Presence of Kallikrein 
Substrate....................................................  173 
M.  Maier,  Z.  Zhegu and B.R.  Binder 
TISSUE  KALLIKREINS,  KININS,  AND  KININASES 
Active Kallikrein,  Preproka11ikrein,  and 
Kallikrein-Inhibitor Complex.................................  181 
J.  Chao,  L.  Chao,  C.M.  Woodley,  W.  Gerald 
and H.S.  Margo1ius 
Characterization of Rat  Kallikrein-Like Mu1tigene 
Family and Its Expression in the 
Submandibular Gland.........................................  189 
L.  Chao,  W.  Gerald and J.  Chao 
Processing of Apo1ipoprotein B-l00 of Human  Plasma 
Low  Density Lipoproteins by Tissue and 
Plasma Ka11ikreins...........................................  195 
A.D.  Cardin,  R.L.  Jackson,  V.H.  Donaldson,  J.  Chao 
and H.S.  Margo1ius 
Transporting Epithelia as Targets  for Kinin Effects................  203 
A.W.  Cuthbert and L.J.  MacVinish 
Purification and Partial Characterization of Cat 
Colon and Submandibular Gland Ka11ikreins....................  211 
H.  Fujimori,  P.R.  Levison and M.  Schachter 
Purification and Partial Characterization of Cat 
Pancreatic and Urinary Ka11ikreins  - Comparison 
With  Other Cat  Tissue Ka11ikreins  and 
Related Proteases............................................  219 
H.  Fujimori,  P.R.  Levison and M.  Schachter 
The  Liver is the Main  Organ to Clear Plasma  and 
Tissue Kallikreins from Rat  Plasma.  In Vivo..................  229 
D.  Borges,  C.  Sampaio,  P.  de  la Llosa and  J.L.  Prado 
Receptor-Mediated Clearance of Tissue Ka1likreins 
by Rat  Liver.................................................  235 
D.R.  Borges,  M.  Kouyoumdjian,  E.S.  Prado 
and J.L.  Prado 
Tissue Kal1ikreins and Related Enzymes: 
Characterization by Model  01igopeptides......................  241 
E.S.  Prado,  L.  Juliano,  M.S.  Araujo-Vie1 
and M.A.  Juliano 
Release of Kallikrein and Tonin  from  the Rat 
Submandibular Gland..........................................  247 
S.R.  Maitra,  S.F.  Rabito and O.A.  Carretero 
Effect of  Sodium Restriction and Corticosteroids on 
Glandular Kallikrein in Plasma  and  in the 
Submandibular Gland..........................................  255 
S.Seto,  S.F.  Rabito.  S.R.  Maitra,  J.N.  Wu 
and O.A.  Carretero
Kallikrein and Kinins  Independently Stimulate Renin 
Release  from  Isolated Rat  Glomeruli..........................  265 
W.H.  Beierwa1tes and O.A.  Carretero 
Regulation of Parotid Kallikrein Secretion-Role 
of the A1pha2- and  Beta-Adrenergic System...................  273 
A.  Rockel,  A.  Preiss1er,  A.  Heid1and 
Effect of Furosemide on  the Rat  Submandibular 
Gland Kallikrein Secretion...................................  279 
O.L.  Catanzaro,  S.B.  Vila,  A.  Zuccolo 
and A.M.  Seeber 
Individual Reaction Steps  in the Release  of Kallidin 
From Kininogen by Tissue Kallikrein..........................  283 
F.  Fiedler,  H.  Hinz  and F.  Lottspeich 
The  Tissue Kallikrein-Kinin System in Human  Seminal 
Plasma - Biochemical  and Functional Aspects..................  291 
E.  Fink,  W.-B.  Schill,  F.  Fiedler,  K.  Shimamoto, 
F.  Krassnigg and J.  Frick 
New  Synthetic Substrate for Kallikrein and 
Its Application..............................................  299 
S.  Fujii, Y.  Hitomi,  K.  Kimura,  M.  Ishii, 
M.  Kurumi  and T.  Aoyama 
Plasma Half-Live  and Organ Uptake  Ratio of 
Radio1abe1ed Glandular Kallikrein in Control 
and Nephrectomized Rats......................................  309 
K.  Nishimura,  T.  Iwata and T.  Kokubu 
Hormonal  Regulation of Glandular Kallikrein Activity 
and  Its Inhibitor in Human  Plasma............................  315 
H.  Koh,  K.  Uchida,  S.  Nambu  and M.  Ikeda 
A Comparative  Study of Proka11ikreins and 
Kallikreins  from Rat  Pancreatic Tissue and Juice.............  323 
A.A.  Jaffa, M.  Hussain,  Z.  Rashid and G.S.  Bailey 
An  Inactive Form  of Kallikrein in Human  Urine......................  329 
K.  Kizuki,  Y.  Shimamoto,  M.  Ikekita and H.  Moriya 
Purification of Inactive Kallikrein from Rat  Urine.................  339 
M.  Takaoka,  H.  Okamura.  T.  Iwamoto  and S.  Morimoto 
Release of Tissue Kallikrein from  the  Isolated 
Perfused Kidney..............................................  347 
N.  Lauar and K.  Bhoola 
Analytical Study of Kallikrein and Kallikrein-Like 
Esterase Activity in Subfractions  from Rat 
Kidney Cortex Microsomes  and  Isolated 
Subce 11u1ar Membranes........................................  355 
K.-J.  Andersen and J.  Ofstad 
Endogenous  Kallikrein Inhibitor in Rat  Kidney 
Cortex-Effect of Glucocorticoid Administration...............  361 
K.  Ito,  K.  Yamada,  S.  Yoshida,  K.  Hasunuma, 
Y.  Tamura  and S.  Yoshida 
x