HISTAMINE-RECEPTORS ON GUINEA-PIG ALVEOLAR MACROPHAGES - CHEMICAL SPECIFICITY AND THE EFFECTS OF H1-RECEPTOR AND H2-RECEPTOR AGONISTS AND ANTAGONISTS

Abstract

Various guinea pig leukocytes were tested for their capacity to bind histamine coupled as a rabbit serum albumin conjugate (H-RSA) to formalized ox red cells. The percentage of rosette-forming target cells was directly related to the concentration of erythrocyte-bound H-RSA. Under optimal experimental conditions the numbers of rosettes varied from 60-81% for alveolar macrophages, 14-73% for peritoneal macrophages, 14-30% for blood monocytes, 27-48% for lymph node cells, 7-24% for blood lymphocytes and 0-29% for peritoneal and blood neutrophils. Virtually no histamine rosettes were formed with eosinophils or basophils. Free histamine partially inhibited rosette formation by alveolar macrophages in a dose-dependent fashion from 10-3 to 10-5 M, and complete inhibition was achieved by the H-RSA conjugate. Amines closely related to histamine such as L-histidine and the major histamine catabolites, imidazoleacetic acid, 1,4-methylhistamine, 1-methyl-4-imidazoleacetic acid and N-acetylhistamine, had no inhibitory effect. The histamine H1-receptor antagonists, mepyramine and chlorpheniramine, and the H1-receptor agonist, 2-(2-aminoethyl) thiazole, all inhibited rosette formation by alveolar macrophages in a dose-dependent fashion. The H2-receptor antagonists, burimamide and metiamide, and the H2-receptor agonists, Dimaprit and 4-methyl-histamine, were inactive. Compared to other leukocytes, histamine receptors are apparently particularly well expressed on the alveolar macrophage. These receptors have a high degree of specificity for histamine in that other amines, closely related chemically, did not inhibit rosette formation. The binding of histamine to the alveolar macrophage membrane is apparently H1- and not H2-receptor dependent.