HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bourne, H. R. Articles by Melmon, K. L. Search for Related Content PubMed Articles by Bourne, H. R. Articles by Melmon, K. L.

Pharmacologic Control of Allergic Histamine Release in Vitro: Evidence for an Inhibitory Role of 3',5'-Adenosine Monophosphate in Human Leukocytes¹

Division of Clinical Pharmacology, Department of Medicine and Pharmacology, University of California Medical Center, San Francisco, California 94122, and the Division of Immunology, Department of Medicine, at the Good Samaritan Hospital, Johns Hopkins University School of Medicine, Baltimore, Maryland 21212

Abstract

The ability of catecholamines, prostaglandins and histamine to stimulate accumulation of 3',5'-adenosine monophosphate (cyclic AMP) in human leukocytes correlated well with their ability to inhibit antigen-induced release of histamine from cells of allergic donors in vitro. In both systems the order of potency of adrenergic agents was characteristic of the beta-receptor (isoproterenol epinephrine norepinephrine phenylephrine), and prostaglandins E₁ and E₂ were equally active, while PGF₁ produced no effect. A beta-adrenergic blocking agent, propranolol, specifically antagonized the effect of catecholamines on both cyclic AMP and histamine release, but had no effect against either the prostaglandins or histamine.

These results strongly support the hypothesis that cyclic AMP acts as a "second messenger" in leukocytes to inhibit allergic release of histamine. Like dibutyryl cyclic AMP and the methylxanthines, all agents which increase synthesis of leukocyte cyclic AMP act to block antigenic histamine release at an early stage of the release process, although the precise mechanism has not yet been defined.

Footnotes

¹ This work was supported by grants from the United States Public Health Service (GM-01791, HE-09964 and AI-07290) Dr. Bourne is an established investigator of the American Heart Association. Dr. Lichtenstein is supported by a Research Career Development Award from the National Institute of Allergy and Infectious Disease.

This paper is publication No. 16 from the O'Neil Research Laboratory of the Good Samaritan Hospital.

This article has been cited by other articles:

				H. R. Bourne, Y. Weinstein, K. L. Melmon, L. M. Lichtenstein, C. S. Henney, and G. M. Shearer Modulation of Inflammation and Immunity by Cyclic AMP Science, April 5, 1974; 184(4132): 19 - 28. [PDF]