Acid-sensing by the T cell death-associated gene 8 (TDAG8) receptor cloned from rat brain

• Published in: Biochemical and biophysical research communications 2009-08, Vol.386 (3), p.420-425
• Main Authors: McGuire, Jennifer, Herman, James P., Ghosal, Sriparna, Eaton, Katherine, Sallee, Floyd R., Sah, Renu
• Format: Article
• Language: English
• Subjects: Acid-Base Equilibrium; Acid-sensing; Amino Acid Sequence; Animals; Brain Ischemia - metabolism; cAMP; Cell Survival; Cloning; Cloning, Molecular; Cyclic AMP - metabolism; Forebrain limbic; Hydrogen-Ion Concentration; Male; Molecular Sequence Data; Panic Disorder - metabolism; pCREB; pH-sensing; Prosencephalon - metabolism; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Signal Transduction; T cell death-associated gene 8; TDAG8
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2009.05.133

The T cell death-associated gene 8 (TDAG8) is a pH-sensing GPCR with a reported immune-specific expression profile. Here, we demonstrate pH-induced activation of TDAG8 receptor cloned from rodent brain (rTDAG8). Cloned rTDAG8 transcript showed 88–95% homology with human and mouse transcripts of lymphoid origin. RT-PCR revealed high expression of TDAG8 in forebrain limbic regions. Extracellular acidification induced significantly elevated intracellular cyclic AMP, and phosphorylated CREB in TDAG8 expressing cells. Acidification-induced LDH release was significantly attenuated in cells expressing TDAG8, suggesting neuroprotective potential against acidosis-related cell injury. Our results open up new areas of investigation into the relevance of TDAG8 in pH homeostasis and pathological states associated with acid–base dys-regulation in the brain such as ischemia and panic disorder.