Mas-related G protein-coupled receptor D is coupled to endogenous calcium-activated chloride channel in Xenopus oocytes.
Mas-related G protein-coupled receptor D (MrgD) is expressed almost exclusively in nociceptive primary sensory neurons and the neurons located in stratum granulosum of skin. More and more evidence suggest that MrgD plays an important role in pain sensation and/or transduction. Recent studies have demonstrated that the receptor is also involved in itch sensation in both mouse and human. In the present study, we identified a robust inward current in MrgD-expressing Xenopus oocytes by using β-alanine, a putative ligand of MrgD. The currents were sensitive to inhibitor of Ca(2+)-activated chloride channels (CaCCs) and intracellular Ca(2+) chelator, suggesting they were produced by endogenous CaCCs. Furthermore, it was demonstrated that upon the application of phospholipase C (PLC) inhibitor, or antisense oligonucleotides of inositol trisphosphate receptor (IP3R), the β-alanine-induced currents were dramatically depressed. However, protein kinase C inhibitor did not display any visible effect on CaCC currents. In summary, our data suggest that the activation of MrgD promotes the open of endogenous CaCCs via G(q)-PLC-IP3-Ca(2+) pathway. The current findings reveal the functional coupling between MrgD and CaCCs in Xenopus oocytes and also provide a facile model to assay the activity of MrgD.
Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Ren-Gong
RG
Zhuo
Xiao-Yun
XY
Ma
Pei-Lan
PL
Zhou
Xiao-Yan
XY
Liu
Kang
K
Zhang
Xiao-Li
XL
Wei
Hai-Tao
HT
Yan
Jiang-Ping
JP
Xu
Jian-Quan
JQ
Zheng
D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis; D015091:beta-Alanine / Q000494:pharmacology / Q000502:physiology
D018118:Chloride Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; C000592696:Mrgprd protein, rat; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; D029867:Xenopus Proteins; D015091:beta-Alanine