Pharmacological analysis of the inflammatory exudate-induced histamine production in bone marrow cells.
The inflammatory exudate at the post-anaphylaxis phase of allergic inflammation in rats has an ability to enhance histamine production by bone marrow cells. To analyze the mechanism of the inflammatory exudate-induced histamine production pharmacologically, the effects of several drugs were examined in cultures of bone marrow cells. Incubation of the bone marrow cells in the presence of the inflammatory exudate that had been centrifuged and dialyzed against Hanks' balanced salt solution increased histidine decarboxylase activity in the cells and histamine concentration in the conditioned medium. The induction of histamine production by the inflammatory exudate was inhibited by actinomycin D (0.01-1 microM), an inhibitor of RNA synthesis, and cycloheximide (0.1-10 microM), a protein synthesis inhibitor. The protein kinase C inhibitors staurosporine (2-20 nM), K-252a (6-200 nM), and H-7 (10.3-103 microM) also inhibited the inflammatory exudate-induced histamine production in a concentration-dependent manner. The tyrosine kinase inhibitor genistein (3.7-37 microM) also inhibited the inflammatory exudate-induced histamine production, but the protein kinase A inhibitor H-89 (0.2 microM), and the adenylate cyclase activator forskolin (0.1 microM) showed no effect. These findings suggest that histamine production induced by the inflammatory exudate is mediated by the de novo synthesis of histidine decarboxylase and by the activation of protein kinase C and tyrosine kinase.
Hirasawa
N
N
Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan. hirasawa@phi.pharm.tohoku.ac.jp
Shiraishi
M
M
Tokuhara
N
N
Hirano
Y
Y
Mizutani
A
A
Mue
S
S
Ohuchi
K
K
D000707:Anaphylaxis / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005122:Exudates and Transudates / Q000276:immunology*; D006632:Histamine / Q000096:biosynthesis*; D006640:Histidine Decarboxylase / Q000378:metabolism; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D006632:Histamine; D003513:Cycloheximide; D011493:Protein Kinase C; D006640:Histidine Decarboxylase