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November 1960

The Metabolism and Functions of Histamine

Author Affiliations
From the Department of Medicine, University of Washington School of Medicine.
Arch Intern Med. 1960;106(5):714-733. doi:10.1001/archinte.1960.03820050126016

Introduction  Few biological agents have received more attention than histamine during the past half-century. This simple chemical was synthesized in 1907 by Windaus and Vogt,1 and was soon identified as a potent pharmacologic agent.2,3 Although histamine is now well recognized as a normal intracellular constituent of many body tissues, years of study were required to establish this fact. Potent vasodilator substances were extractable from animal tissues, but the identity of any with histamine was difficult to prove.4 Two decades of research were required to establish the importance of intracellular histamine and the physiological significance of its release. Of note were the classical observations of Thomas Lewis on the whealing response in human skin 5 and the studies by H. H. Dale on cellular histamine so nicely described in his Croonian lectures of 1929.6 Dale suggested that antigen-antibody reactions might release histamine, but he also emphasized the many differences between the

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Pickering, G.:  Observations on the Mechanism of Headache Produced by Histamine ,  Clin. Sc. 1:77-101, 1933.
Weiss, S.; Robb, G. P., and Blumgart, H. L.:  The Velocity of Blood Flow in Health and Disease as Measured by the Effect of Histamine on the Minute Vessels ,  Am. Heart J. 4: 664-691, 1929.
Curry, J. J., and Lowell, F. C.:  Measurement of Vital Capacity in Asthmatic Subjects Receiving Histamine and Acetyl-Beta-Methyl Choline ,  J. Allergy 19:9-18, 1948.
Bouhuys, A.; Jönsson, R.; Lichtneckert, S.; Lindell, S.-E.; Lundgren, C.; Lundin, G., and Ringquist, T. R.:  Effects of Histamine on Pulmonary Ventilation in Man ,  Clin. Sc. 19:79-94, 1960.
Code, C. F.:  Histamine and Gastric Secretion , in  Ciba Foundation Symposium, Histamine , edited by G. E. W. Wolstenholme and C. M. O'Connor, Boston, Little, Brown & Company, 1956, pp. 189-219.
Boyer, J.; Depierre, F.; Tissier, M., and Jacob, J.:  Mass Histamine Poisoning Due to Ingestion of Tuna Fish ,  Presse méd. 64:1003-1004, 1956.
McElin, T. W., and Horton, B. T.:  The Administration of Histamine During Pregnancy: Apparent Lack of a Clinical Oxytocic Effect with Small Doses ,  Am. J.M. Sc. 218:432-438, 1949.
VanArsdel, P. P., Jr., and Sherman, W. B.:  The Risk of Inducing Constitutional Reactions in Allergic Patients ,  J. Allergy 28:251-261, 1957.
Manger, W. M.; Wakim, K. G., and Bollman, J. L.:  Chemical Quantitation of Epinephrine and Norepinephrine in Plasma , Springfield, Ill., Charles C Thomas, Publisher, 1959, pp. 231, 324.
Trendelenburg, U.:  The Action of Histamine and Pilocarpine on the Superior Cervical Ganglion and the Adrenal Glands of the Cat ,  Brit. J. Pharmacol. 9:481-487, 1954.
Roth, G. M., and Kvale, W. F.:  A Tentative Test for Phenochromocytoma ,  Am. J.M. Sc. 210:653-660, 1945.
Herbertson, B. M.:  Patchy Myocardial Necroses in Rabbits after Shock Doses of Histamine and Peptone ,  J. Path. & Bact. 72:137-141, 1956.
Papacostas, C. A.; Mozden, P., and Lowe, E. R.:  Effect of Histamine and Histamine Liberator, Compound 48/80 on Blood Glucose ,  Proc. Soc. Exper. Biol. & Med. 97:297-299, 1958.
Bierman, H. R.; Kelly, K. H.; Petrakis, N. L.; Cordes, F.; Foster, M., and Lose, E.:  The Effect of Intravenous Histamine Administration on the Level of the White Blood Count in the Peripheral Blood ,  Blood 6:926-935, 1951.
Bierman, H. R.; Kelly, K.; Cordes, F., and Coblentz, A.:  The Influence of Histamine upon the Circulating Leukocyte Level in Patients with the Leukemias ,  Blood 11:708-719, 1956.
von Euler, U. S.:  Histamine and Nerves , in  Ciba Foundation Symposium, Histamine , edited by G. E. W. Wolstenholme and C. M. O'Connor, Boston, Little, Brown & Company, 1956, pp. 235-241.
Whelan, R. F.:  Histamine and Vasodilatation , in  Ciba Foundation Symposium, Histamine , edited by G. E. W. Wolstenholme and C. M. O'Connor, Boston, Little, Brown & Company, 1956, pp. 220-234.
Scherbel, A. L.; McKittrick, R. L., and Hawk, W. A.:  Effect of Serotonin and Histamine on Connective Tissue in the Rat ,  Clin. Res. 7: 395, 1959.
Boyd, J. F., and Smith, A. N.:  The Effect of Histamine and a Histamine-Releasing Agent (Compound 48/80) on Wound Healing ,  J. Path. & Bact. 78:379-388, 1959.
Kahlson, G.:  A Place for Histamine in Normal Physiology ,  Lancet 1:67-71, 1960.
Michelson, A. L., and Lowell, F. C.:  Antihistaminic Drugs ,  New England J. Med. 258:994-1000, 1958.
Cirqua, S.: Quoted by Randolph and Rackemann.37
Mitchell, R. G.; Butt, H. R., and Code, C. F.:  Histamine Metabolism in Diseases of the Liver ,  J. Clin. Invest. 33:1199-1203, 1954.
Anrep, G. V., and Barsoum, G. S.:  Blood Histamine in Experimental Obstruction of the Common Bile Duct ,  J. Physiol. 120:427-430, 1953.
Irvine, W. f.; Duthie, H. L.; Ritchie, H. D., and Waton, N. G.:  The Liver's Role in Histamine Absorption from the Alimentary Tract ,  Lancet 1:1064-1069, 1959.
Parrot, J. L., and Laborde, C.:  Le Pouvoir histaminopexique du Sérum sanguin son absence chez les sujets allergiquis ,  Presse méd. 61:1267-1269, 1953.
Wodniansky, P.:  Histamine Fixation, Foreign Letters (Austria) ,  J.A.M.A. 165:2104, 1957.
Code, C. F.: Personal communication to the authors.
Kaplan, E. H., and Davis, J.:  Binding of Histamine by Animal Proteins ,  Proc. Soc. Exper. Biol. & Med. 84:218-220, 1953.
Nickel, W. R.:  Urticaria Pigmentosa ,  A.M.A. Arch. Dermat. 76:476-498, 1957.
Reilly, E. B.; Shintani, J., and Goodman, J.:  Systemic Mast-Cell Disease with Urticaria Pigmentosa ,  A.M.A. Arch. Dermat. 71:561-569, 1955.
Berlin, C.:  Urticaria Pigmentosa as a Systemic Disease ,  A.M.A. Arch. Dermat. 71:703-712, 1955.
Sagher, F.; Liban, E.; Ungar, H., and Schorr, S.:  Urticaria Pigmentosa with Bone Involvement: Mast Cell Aggregates in Bones and Myelosclerosis Found at Autopsy in a Case Dying of Monocytic Leukemia ,  J. Invest. Dermat. 27: 355-368, 1956.
Lowenthal, M.; Schen, R. J.; Berlin, C., and Wechsler, L.:  Urticaria Pigmentosa with Systemic Mast-Cell Disease ,  A.M.A. Arch. Dermat. 75:512-516, 1957.
Rider, T. L.; Stein, A. A., and Abbuhl, J. W.:  Generalized Mast Cell Disease and Urticaria Pigmentosa ,  Pediatrics 19:1023-1032, 1957.
Fadem, R. S.:  Tissue Mast Cells in Human Bone Marrow ,  Blood 6:614-630, 1951.
Waters, W. J., and Lacson, P. S.:  Mast Cell Leukemia Presenting as Urticaria Pigmentosa ,  Pediatrics 19:1033-1042, 1957.
Efrati, P.; Klajman, A., and Spitz, H.:  Mast Cell Leukemia?—Malignant Mastocytosis with Leukemia-Like Manifestations ,  Blood 12:869-882, 1957.
Gardner, L. I., and Tice, A. A.:  Histamine and Related Compounds in Urticaria Pigmentosa: Analyses of Tissues Having Mast-Cell Infiltration ,  Pediatrics 21:805-812, 1958.
Marshall, J.; Walker, J.; Lurie, H. I.; Hansen, J. D. L., and Mackenzie, D.:  Solitary Mastocytoma and the Mastocytoses: A Discussion of the Mastocytoses and a Report of 2 Cases of Solitary Mastocytoma Showing an Unusual Phenomenon of Generalized Flushing ,  S. African M.J. 31:867-876, 1957.
Ende, N., and Cherniss, E. I.:  Splenic Mastocytosis ,  Blood 13:631-641, 1958.
Hamrin, B.:  Release of Histamine in Urticaria Pigmentosa ,  Lancet 2:857-863, 1957.
Brogren, N.; Dunér, H.; Hamrin, B.; Pernow, B.; Theander, G., and Waldenström, J.:  Urticaria Pigmentosa (Mastocytosis): A Study of 9 Cases with Special Reference to the Excretion of Histamine in Urine ,  Acta med. scandinav. 163: 223-233, 1959.Crossref
Horton, B. T.:  Histaminic Cephalalgia ,  J.A.M.A. 160:468-469, 1956.Crossref
Robinson, B. W.:  Histaminic Cephalgia ,  Medicine 37:161-180, 1958.Crossref
Gardner, F. H., and Diamond, L. K.:  Autoerythrocyte Sensitization ,  Blood 10:675-690, 1955.
Shulman, N. R.; Feigen, J. H., and Bithell, T. C.:  The Role of Histamine in the Pathogenesis of a Disease Characterized by Ecchymoses and Systemic Symptoms ,  Clin. Res. 7:216, 1959.
Ambrus, J. L.; Ambrus, C. M., and Harrison, J. W. E.:  Effect of Histamine Desensitization on Histamine Induced Gastric Secretion of Guinea Pigs ,  Gastroenterology 18:249-253, 1951.
Wells, J. A.; Gray, J. S., and Dragstedt, C. A.:  An Investigation of the Question of Histamine Tolerance ,  J. Allergy 13:77-84, 1941.Crossref
Jonez, H. D.:  The Use of Histamine in the Treatment of Allergic Diseases ,  Ann. Allergy 10:454-464, 1952.
Shelden, C. H., and Horton, B. T.:  Treatment of Ménière's Disease with Histamine Administered Intravenously ,  Proc. Staff Meet. Mayo Clin. 15:17-21, 1940.
Fell, N.; Rodney, G., and Marshall, D. E.:  Histamine-Protein Complexes: Synthesis and Immunologic Investigation; Histamine—Azoprotein ,  J. Immunol. 47:237-249, 1943.
 Symposium on Histamine ,  J. Allergy 18: 1, 7, 13, 1947.Crossref
Bernstein, B. M.:  Histamine in the Treatment of Peptic Ulcer ,  Ann. Int. Med. 26:852-857, 1947.Crossref