Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously showed that the mood stabilizers lithium, valproate (VPA), and carbamazepine (CBZ) have a common, inositol-reversible effect on the dynamic behavior of sensory neurons, suggesting that they all inhibit phosphoinositide (PIns) synthesis. We now report similar effects of the drugs in cortical neurons and show by mRNA analysis that these neurons do not express myo-inositol-1-phosphate synthase (MIP-synthase) or the sodium-dependent myo-inositol transporters (SMIT1 and SMIT2), but they do express the H+/myo-inositol transporter (HMIT) mRNA and protein. We used glycogen synthase kinase-3 (GSK3) inhibitors and Western blotting of GSK3 targets to confirm that the common effects of the drugs on both sensory and cortical neuron growth cones are inositol-dependent and GSK3-independent. Moreover, the anti-convulsant drugs gabapentin and phenytoin do not mimic the mood stabilizers. These results confirm that the common inositol-reversible effect of mood stabilizers on neurons does not involve GSK3 and further show that the effects are independent of MIP-synthase and SMIT transporters.
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PMID:The common inositol-reversible effect of mood stabilizers on neurons does not involve GSK3 inhibition, myo-inositol-1-phosphate synthase or the sodium-dependent myo-inositol transporters. 1653 Oct 65

Phosphoinositide signalling regulates a series of important neuronal processes that are thought to be altered in mood disorders. Furthermore, mood-stabilizing drugs inhibit key enzymes that regulate phosphoinositide production and alter neuronal growth cone morphology in an inositol-reversible manner. Inositol is taken up by neurons from the extracellular fluid, presumably via membrane transporters; it can also be synthesized by the enzyme MIP-synthase (myo-inositol-1-phosphate synthase) and, in addition, it is generated by inositol phospholipid hydrolysis. The neuronal-specific HMIT (H(+)-myo-inositol transporter) represents a potential regulator of inositol signalling in neurons that warrants further investigation.
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PMID:Investigation of the H(+)-myo-inositol transporter (HMIT) as a neuronal regulator of phosphoinositide signalling. 1975 67