Identification of the Na+/H+ exchanger 1 in dorsal root ganglion and spinal cord: its possible role in inflammatory nociception.

mRNA and protein presence of Na+/H+ exchanger (NHE) 1 (NHE1) and 5 (NHE5) in dorsal root ganglion (DRG) and dorsal spinal cord as well as its possible role in three inflammatory nociception tests were determined. Local peripheral ipsilateral, but not contralateral, administration of NHE inhibitors 5-(N,N-dimethyl)amiloride hydrochloride (DMA, 0.3-30 microM/paw), 5-(N-ethyl-N-isopropyl)amiloride (EIPA, 0.3-30 microM/paw) and amiloride (0.1-10 microM/paw) significantly increased flinching but not licking behavior in the capsaicin and 5-HT tests. Moreover, DMA and EIPA (0.03-30 microM/paw) as well as amiloride (0.1-1 microM/paw) augmented, in a dose-dependent manner, 0.5% formalin-induced flinching behavior during phase II but not during phase I. Reverse transcription-polymerase chain reaction showed the expression of NHE1 and NHE5 in DRG and dorsal spinal cord. Western blot analysis confirmed the presence of NHE1 in DRG and spinal cord. Moreover, NHE5 was expressed in dorsal spinal cord, but not in DRG where a 45 kDa truncated isoform of NHE5 was identified. Collectively, these data suggest that NHE1, but not NHE5, plays an important role reducing inflammatory pain in rats.

Excitatory amino acid-induced AP-1 DNA binding activity in Müller glia.

The effect of L-glutamate (L-Glu) and its structural analogs N-methyl-D-aspartate (NMDA), quisqualate (QA), and kainate (KA) on the DNA binding activity of the Activator Protein 1 (AP-1) and the Ca2+/cAMP Responsive Element Binding Protein (CREB) families of transcription factors was examined in cultured chick retinal Müller glia cells. L-Glu, NMDA, and KA evoked a dose and time dependent increase in AP-1 DNA binding activity and had no effect on CREB binding. The order of potency for stimulating AP-1 DNA binding was NMDA > or = Glu > KA >> QA. L-Glu responses were partially blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and by 3-[RS)-2-carboxypiperazin-4-yl)]-propyl-1-phosphonate (CPP) indicating that the increase in DNA binding is mediated both by an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/low affinity KA and a NMDA subtypes of L-Glu receptors. Since Müller glia L-Glu receptors are probably mediators of the efficacy of the excitatory transmission in the retina, the present findings suggest that a stimulus-transcription coupling triggered by L-Glu in the glial cells might have a role in the long-term modulation of these synapses.