title: Hydrogen sulfide regulates intracellular pH in rat primary cultured glia cells.
abstract: Intracellular pH (pH(i)) plays an important role in the regulation of central nervous system function. In the present study, we examined whether hydrogen sulfide (H(2)S), a recently recognized neuromodulator, regulates pH(i) in rat primary cultured glia cells. pH(i) was measured with a fluorescent sensitive dye, BCECF-AM. Activities of Cl(-)/HCO(3)(-) exchanger and Na(+)/H(+) exchanger were examined by assessing their capacities to load or extrude H(+) upon NH(4)Cl pulse load. We found that NaHS, a H(2)S donor, decreased pH(i) in a concentration-dependent manner ranging from 10 to 200muM in the primary cultured microglia. Blockade of the Cl(-)/HCO(3)(-) exchanger with, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or Na(+)/H(+) exchanger with 5-N-methyl-N-isobutylamiloride (MIA) significantly attenuated the pH(i)-lowering effect of NaHS. Moreover, NaHS significantly increased the activity of Cl(-)/HCO(3)(-) exchanger but inhibited that of Na(+)/H(+) exchanger. The pH regulatory effect of H(2)S was also observed in primary cultured astrocytes, but not in SH-SY5Y neuronal cells. In conclusion, we found for the first time that H(2)S induced intracellular acidification in glia cells via regulation of the activities of Cl(-)/HCO(3)(-) exchanger and Na(+)/H(+) exchanger. The present study may provide new evidence for H(2)S to serve as a neuromodulator and offer a potential approach for the treatment of neurological diseases.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu 210029, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Chooi Hoong
authors.initials: CH
authors.lastname: Choo
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Hu
authors.forename: Boon Hian
authors.initials: BH
authors.lastname: Tan
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Bian
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000393:Air Pollutants / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D007424:Intracellular Fluid / Q000187:drug effects*; D009447:Neuroblastoma; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000393:Air Pollutants; D027963:Chloride-Bicarbonate Antiporters; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D006862:Hydrogen Sulfide