Acid-sensing by the T cell death-associated gene 8 (TDAG8) receptor cloned from rat brain.
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.
McGuire
Jennifer
J
Department of Psychiatry, University of Cincinnati, Genome Research Institute, 2170 East Galbraith Road, Cincinnati, OH 45237, USA.
Herman
James P
JP
Ghosal
Sriparna
S
Eaton
Katherine
K
Sallee
Floyd R
FR
Sah
Renu
R
D000136:Acid-Base Equilibrium; D000595:Amino Acid Sequence; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D002470:Cell Survival; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D008969:Molecular Sequence Data; D016584:Panic Disorder / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
C542490:GPR65 protein, rat; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP