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Decreased H2 histamine response of granulocytes of asthmatic patients.
Busse WW, Sosman J
(1977) J Clin Invest 59: 1080-7
MeSH Terms: Adult, Asthma, Bronchitis, Chlorpheniramine, Cyclic AMP, Dose-Response Relationship, Drug, Female, Glucuronidase, Histamine, Humans, Isoproterenol, Lysosomes, Male, Middle Aged, Neutrophils, Propranolol, Receptors, Histamine, Receptors, Histamine H2, Zymosan
Show Abstract · Added March 5, 2014
Increased bronchial sensitivity to inhaled histamine in asthma is well known. The mechanism of this increased bronchial sensitivity is not known nor has it been demonstrated that isolated cells respond abnormally to histamine. Polymorpho-nuclear leukocytes (PMNs) provide a homogeneous cell population to study agonist response. Release of granulocyte lysosomal enzymes is inhibited by agonists increasing the PMN cyclic AMP concentration. The release of the lysosomal enzyme beta glucuronidase by serum-activated particles of zymosan was similar in PMNs isolated from normal and asthma subjects. Histamine (100-0.01 muM) inhibited enzyme release. Except at the maximal concentration of histamine (100 muM), the response to histamine was decreased in asthma. The inhibition of enzyme release paralleled an increase in intracellular PMN cyclic AMP. In asthma, the cyclic AMP response to histamine was reduced. The H2 antihistamine metiamide blocked histamine inhibition of lysosomal enzyme release and the increase in cyclic AMP. The effect was maximal at concentrations equimolar to those of histamine. The H1 antihistamine chlorpheniramine had no effect on histamine inhibition of granulocyte lysosomal enzyme release. A decrease in the inhibition of the release of the inflammatory lysosomal enzymes from granulocytes in asthma may contribute to an enhanced bronchial inflammatory reaction.
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19 MeSH Terms
Histamine inhibition of neutrophil lysosomal enzyme release: an H2 histamine receptor response.
Busse WW, Sosman J
(1976) Science 194: 737-8
MeSH Terms: Cyclic AMP, Enzyme Activation, Glucuronidase, Histamine, Humans, Inflammation, Lysosomes, Metiamide, Neutrophils, Receptors, Histamine, Receptors, Histamine H2, Zymosan
Show Abstract · Added March 5, 2014
Human polymorphonuclear leukocytes treated with cytochalasin B release the lysosomal enzyme beta glucuronidase during contact with serum-activated zymosan particles. Histamine increases intracellular cyclic adenosine monophosphate and inhibits release of this enzyme. The H2 antihistamine metiamide blocks the histamine inhibition of lysosomal enzyme release and the increase in the intracellular adenoisine 3,5'-monophosphate of granulocytes. Chlorpheniramine, an H1 antihistamine, did not block the histamine inhibition of granulocyte lysosomal enzyme release.
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12 MeSH Terms