Effect of deuterium oxide (D2O) on the IgE-mediated Ca2+ influx, arachidonic acid and histamine release in rat basophilic leukemia cells.
Deuterium oxide (D2O), which is known to stimulate microtubule aggregation, enhanced the IgE-mediated 45Ca2+ influx, (14C)-arachidonic acid and histamine release in rat basophilic leukemia cells (RBL-2H3) in the same dose-dependent manner (up to 90% (v/v]. We compared the interaction between D2O and a variety of groups of pharmacological agents. A microtubule depolymerizing agent, demecolcine, which inhibited the IgE-mediated (14C)-arachidonic acid and histamine release without affecting 45Ca2+ influx, was counteracted by 45% D2O. Taxol, a microtubule stabilizing agent, which had an inhibitory effect on the above three steps, was also reversed by 45% D2O. These results would support the previous data on the interaction between D2O and microtubules and would further suggest that the status of microtubule aggregation may be related to the secretory process. Calmodulin inhibitors (W-7, trifluoperazine) blocked the IgE-mediated 45Ca2+ influx, (14C)-arachidonic acid and histamine release in the same dose-dependent manner, but were counteracted by 45% D2O. In contrast, the effects of proteinase inhibitors (TPCK, TLCK), an adenylate cyclase inhibitor (ddAdo), a phosphodiesterase inhibitor (aminophylline), a phospholipid methylation inhibitor (DZA + Hcy) and microfilament blockers (cytochalasin B and D) were not counteracted by 45% D2O. These results would suggest that D2O may be associated with calmodulin directly or indirectly possibly through some relationship between calmodulin and microtubules.
Urata
C
C
Watanabe
A
A
Ogawa
Y
Y
Takei
N
N
Nomoto
H
H
Mizobe
M
M
Abe
Y
Y
Mano
K
K
Urata
S
S
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001491:Basophils / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003903:Deuterium / Q000494:pharmacology*; D017666:Deuterium Oxide; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release; D007073:Immunoglobulin E / Q000502:physiology; D007942:Leukemia, Experimental / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured; D014867:Water / Q000494:pharmacology*
D001095:Arachidonic Acids; D014867:Water; D007073:Immunoglobulin E; D003903:Deuterium; D017666:Deuterium Oxide; D002118:Calcium