Chronic alteration in phosphatidylinositol 4,5-biphosphate levels regulates XXXX and mustard oil responses.

@entity32 @entity1078 @entity2951 @entity13811 @entity164 @entity158 @entity1076 @entity435 @entity13812
There is an agreement that acute (in minutes) hydrolysis and accumulation of @entity1078 ( @entity1078 ) modulate @entity13812 and @entity13811 activities. Because @entity32 results in PIP(2) depletion, persisting for long periods (hours to days) in @entity158 models and in the clinic, we examined whether chronic depletion and accumulation of PIP(2) affect @entity2951 (CAP) and mustard oil (MO) responses. In addition, we wanted to evaluate whether the effects of @entity1078 depend on @entity13812 and @entity13811 coexpression and whether the PIP(2) actions vary in expression cells vs. sensory neurons. Chronic @entity1078 production was stimulated by overexpression of @entity1076 -5-kinase, and PIP(2) -specific phospholipid 5'-phosphatase was selected to reduce plasma membrane levels of @entity1078 . Our results demonstrate that CAP (100 nM) responses and receptor tachyphylaxis are not significantly influenced by chronic changes in @entity1078 levels in @entity164 ( @entity164 ) or @entity13811 null-mutant sensory neurons as well as CHO cells expressing @entity13812 alone or with @entity13811 . However, low concentrations of CAP (20 nM) produced a higher response after PIP(2) depletion in cells containing @entity13812 alone but not @entity13812 together with @entity13811 . MO (25  M) responses were also not affected by PIP(2) in @entity164 sensory neurons and cells coexpressing @entity13811 and @entity13812 . In contrast, @entity1078 reduction leads to pronounced tachyphylaxis to MO in cells with both channels. Chronic effect of @entity1078 on @entity13811 activity depends on presence of the @entity13812 channel and cell type ( @entity435 vs. sensory neurons). In summary, chronic alterations in PIP(2) levels regulate magnitude of CAP and MO responses as well as MO tachyphylaxis. This regulation depends on coexpression profile of @entity13811 and @entity13812 and cell type.
