TY - JOUR
T1 - Stimulation of histamine release and arachidonic acid metabolism in rat peritoneal mast cells by thapsigargin, a non-TPA-type tumor promoter
AU - Ohuchi, Kazuo
AU - Takahashi, Chikako
AU - Hirasawa, Noriyasu
AU - Watanabe, Masako
AU - Fujiki, Hirota
AU - Tsurufuji, Susumu
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas (63614501 to K.O.) from the Ministry of Education, Science and Culture of Japan, and by a grant (to K.O.) from the Ministry of Health and Welfare of Japan. We are grateful to Dr. S. B. Christensen, Royal Danish School of Pharmacy, Denmark, for providing thapsigargin, and to Dr. L. Levine, Brandeis University, MA, U.S.A. for providing prostaglandin D2 anti-serum. We are also grateful to Dr. P.J. McHale, The Wellcome Research Laboratories, Beckenham, U.K. for providing BW755C, and to Dr. S. Terao, Takeda Pharmaceutical Ind., Osaka, Japan, for providing AA861.
PY - 1989/5/15
Y1 - 1989/5/15
N2 - Thapsigargin, a non-TPA-type tumor promoter, releases histamine and stimulates arachidonic acid metabolism in rat peritoneal mast cells. In order to clarify the relationship between the histamine-releasing activity and the arachidonic acid metabolism-stimulating activity of thapsigargin in mast cells, the effects of cyclooxygenase inhibitors, indomethacin and ibuprofen, a lipoxygenase inhibitor, AA861, and dual inhibitors for cyclooxygenase and lipoxygenase, nordihydroguaiaretic acid and BW755C, on histamine release and arachidonic acid metabolism were examined. High-performance liquid chromatography analysis revealed that the peritoneal mast cells preferentially produce prostaglandin D2 by thapsigargin treatment. These inhibitors suppressed thapsigargin-induced prostaglandin D2 production in a dose-dependent manner, but failed to inhibit histamine release, suggesting that the mechanisms for stimulation of histamine release by thapsigargin is not dependent on increased arachidonic acid metabolism. Time-course experiments of histamine release and the release of radioactivity from [3H]arachidonic acid-labeled mast cells also provide evidence for a difference in mechanism.
AB - Thapsigargin, a non-TPA-type tumor promoter, releases histamine and stimulates arachidonic acid metabolism in rat peritoneal mast cells. In order to clarify the relationship between the histamine-releasing activity and the arachidonic acid metabolism-stimulating activity of thapsigargin in mast cells, the effects of cyclooxygenase inhibitors, indomethacin and ibuprofen, a lipoxygenase inhibitor, AA861, and dual inhibitors for cyclooxygenase and lipoxygenase, nordihydroguaiaretic acid and BW755C, on histamine release and arachidonic acid metabolism were examined. High-performance liquid chromatography analysis revealed that the peritoneal mast cells preferentially produce prostaglandin D2 by thapsigargin treatment. These inhibitors suppressed thapsigargin-induced prostaglandin D2 production in a dose-dependent manner, but failed to inhibit histamine release, suggesting that the mechanisms for stimulation of histamine release by thapsigargin is not dependent on increased arachidonic acid metabolism. Time-course experiments of histamine release and the release of radioactivity from [3H]arachidonic acid-labeled mast cells also provide evidence for a difference in mechanism.
KW - (Rat peritoneal mast cell)
KW - Arachidonic acid metabolism
KW - Histamine release
KW - Prostaglandin D
KW - Thapsigargin
UR - http://www.scopus.com/inward/record.url?scp=0024561952&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024561952&partnerID=8YFLogxK
U2 - 10.1016/0005-2760(89)90091-X
DO - 10.1016/0005-2760(89)90091-X
M3 - Article
C2 - 2469475
AN - SCOPUS:0024561952
SN - 0005-2760
VL - 1003
SP - 9
EP - 14
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 1
ER -