| First Author | Rocha MA | Year | 2008 |
| Journal | J Neurochem | Volume | 106 |
| Issue | 1 | Pages | 231-43 |
| PubMed ID | 18363831 | Mgi Jnum | J:137321 |
| Mgi Id | MGI:3798757 | Doi | 10.1111/j.1471-4159.2008.05355.x |
| Citation | Rocha MA, et al. (2008) Na(+)/H(+) exchanger inhibition modifies dopamine neurotransmission during normal and metabolic stress conditions. J Neurochem 106(1):231-43 |
| abstractText | Na(+)/H(+) exchanger (NHE) proteins are involved in intracellular pH and volume regulation and may indirectly influence neurotransmission. The abundant NHE isoform 1 (NHE1) has also been linked to brain cell damage during metabolic stress. It is not known, however, whether NHE1 or other NHE isoforms play a role in striatal dopamine (DA) neurotransmission under normal or metabolic stress conditions. Our study tested the hypothesis that NHE inhibition with cariporide mesilate (HOE-642) modifies striatal DA overflow and DAergic terminal damage in mice caused by the mitochondrial inhibitor malonate. We also explored the expression of NHE1-5 in the striatum and substantia nigra. Reverse microdialysis of HOE-642 elicited a transient elevation followed by a reduction in DA overflow accompanied by a decline in striatal DA content. HOE-642 pre-treatment diminished the malonate-induced DA overflow without reducing the intensity of the metabolic stress or subsequent DAergic axonal damage. Although NHE isoforms 1-5 are expressed in the striatum and midbrain, NHE1 protein was not co-located on nigrostriatal DAergic neurons. The absence of NHE1 co-location on DAergic neurons suggests that the effects of HOE-642 on striatal DA overflow are either mediated via NHE1 located on other cell types or that HOE-642 is acting through multiple NHE isoforms. |
