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PMID:18195371
| Citation |
Park, L, Gallo, EF, Anrather, J, Wang, G, Norris, EH, Paul, J, Strickland, S and Iadecola, C (2008) Key role of tissue plasminogen activator in neurovascular coupling. Proc. Natl. Acad. Sci. U.S.A. 105:1073-8 |
|---|---|
| Abstract |
The increase in blood flow evoked by synaptic activity is essential for normal brain function and underlies functional brain imaging signals. Nitric oxide, a vasodilator released by NMDA receptor activation, is critical for the flow increase, but the factors linking NMDA receptor activity to nitric oxide-dependent hyperemia are poorly understood. Here, we show that tissue plasminogen activator (tPA), a serine protease implicated in NMDA receptor signaling, is required for the flow increase evoked by somatosensory stimulation. tPA acts by facilitating neuronal nitric oxide release, but this effect does not involve enhancement of NMDA currents or the associated intracellular Ca(2+) rise. Rather, the evidence suggests that tPA controls NMDA-dependent nitric oxide synthesis by influencing the phosphorylation state of neuronal nitric oxide synthase. These findings unveil a previously unrecognized role of tPA in vital homeostatic mechanisms coupling NMDA receptor signaling with nitric oxide synthesis and local cerebral perfusion. |
| Links |
PubMed PMC2242693 Online version:10.1073/pnas.0708823105 |
| Keywords |
Animals; Calcium/metabolism; Electrophysiology; Hyperemia/chemically induced; Hyperemia/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; N-Methylaspartate/pharmacology; Neurons/metabolism; Neurons/secretion; Nitric Oxide/secretion; Nitric Oxide Synthase Type I/metabolism; Patch-Clamp Techniques; Phosphorylation; Receptors, N-Methyl-D-Aspartate/metabolism; Regional Blood Flow; Tissue Plasminogen Activator/deficiency; Tissue Plasminogen Activator/genetics; Tissue Plasminogen Activator/metabolism |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
part_of |
GO:0005912: adherens junction |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
Notes
See also
References
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