We sought to further elucidate signal transduction pathways for the I(1)- @entity947 receptor in PC12 cells and their interaction with the well-characterized signaling events triggered by nerve growth factor (NGF) in these cells. Stimulation of the I(1)- @entity947 receptor with @entity23703 , a centrally acting antihypertensive, increased by greater than two-fold the proportion of @entity10861 and @entity31706 in the phosphorylated active form. Similarly, NGF elicited a five-fold increase in activated ERKs. Surprisingly, treatment of NGF-treated cells with @entity23703 completely reversed activation of @entity2509 . @entity23703 -induced inhibition of @entity2509 activation in NGF-treated cells was dose-dependent, followed a limited time course and could be blocked by the I(1)-antagonist @entity26276 . These data suggested possible deactivation of @entity2509 by specific phosphatases. Therefore, we assayed levels of @entity70355 , a dual specificity phosphatase whose substrates include @entity2509 . @entity23703 and NGF both increased levels of @entity70355 by three-fold. These effects were additive, as both agents together increased @entity70355 by a total of six-fold. @entity23703 -induced induction of @entity70355 was time- and dose-dependent and could be blocked by the I(1)-antagonist efaroxan or by D609, an inhibitor of @entity2434 -selective phospholipase C known to block downstream signaling events coupled to I(1)-receptors. Thus, I(1)-receptors can abrogate the primary signaling cascade activated by NGF, most likely by increasing levels of a specific phosphatase to return dually phosphorylated @entity2509 to its unphosphorylated state.

The I(1)- XXXX receptor in PC12 pheochromocytoma cells reverses NGF-induced @entity2509 activation and induces @entity70355 phosphatase.

@entity10861 :: ('50689(Tax:10116)', 'Gene') :: ['ERK-1'] @entity23703 :: ('MESH:C043482', 'Chemical') :: ['moxonidine', 'Moxonidine'] @entity2509 :: ('24338(Tax:10116)', 'Gene') :: ['ERK'] @entity2434 :: ('MESH:D010713', 'Chemical') :: ['phosphatidylcholine'] @entity26276 :: ('MESH:C062597', 'Chemical') :: ['efaroxan'] @entity31706 :: ('116590(Tax:10116)', 'Gene') :: ['ERK-2'] @entity70355 :: ('60587(Tax:10116)', 'Gene') :: ['MKP-2'] @entity947 :: ('CHEBI:53094', 'Chemical') :: ['imidazoline']
@entity947 :: (CHEBI:53094,Chemical) :: ['imidazoline']
