Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.16.2 (
PCP
)
3,761
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We investigated changes in signal transduction via calcineurin (CaN) in the striatum of rats behaviorally sensitized to methamphetamine (Meth). The rats were injected with Meth (4 mg/kg, s.c.) five times a week for 3 weeks and then were given a challenge dose of Meth (2 mg/kg, s.c.). Seven days after the challenge test, we determined the levels of CaN Aalpha and Abeta by Western blotting. We further immunoquantified
DARPP-32
(dopamine- and cAMP-regulated phosphoprotein, mw 32,000) and phosphothreonine-
DARPP-32
, which can be dephosphorylated at threonine sites by CaN. We found that both CaN Aalpha and Abeta were significantly decreased in the particulate fractions but were not changed in the soluble fractions from the striatum of Meth-sensitized rats as compared with control rats. The same findings were observed in the striatum of rats 6 h after the injection of
PCP
(10 mg/kg, s.c.). In the striatum of Meth-sensitized rats, phosphothreonine-
DARPP-32
immunoreactivities significantly increased, but
DARPP-32
immunoreactivities were not significantly different from those of the control rats. These results indicate that the activity of signal transduction via CaN is functionally decreased in the striatum of Meth-sensitized rats.
...
PMID:Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine. 1195 50
Three distinct classes of drugs: dopaminergic agonists (such as D-amphetamine), serotonergic agonists (such as LSD), and glutamatergic antagonists (such as
PCP
) all induce psychotomimetic states in experimental animals that closely resemble schizophrenia symptoms in humans. Here we implicate a common signaling pathway in mediating these effects. In this pathway, dopamine- and an adenosine 3',5'-monophosphate (cAMP)-regulated phospho-protein of 32 kilodaltons (
DARPP-32
) is phosphorylated or dephosphorylated at three sites, in a pattern predicted to cause a synergistic inhibition of protein phosphatase-1 and concomitant regulation of its downstream effector proteins glycogen synthesis kinase-3 (GSK-3), cAMP response element-binding protein (CREB), and c-Fos. In mice with a genetic deletion of
DARPP-32
or with point mutations in phosphorylation sites of
DARPP-32
, the effects of D-amphetamine, LSD, and
PCP
on two behavioral parameters-sensorimotor gating and repetitive movements-were strongly attenuated.
...
PMID:Diverse psychotomimetics act through a common signaling pathway. 1524 57
