PT  - JOURNAL ARTICLE
AU  - Elena Deliu
AU  - Margaret Sperow
AU  - Linda Console-Bram
AU  - Rhonda L. Carter
AU  - Douglas G. Tilley
AU  - Daniel J. Kalamarides
AU  - Lynn G. Kirby
AU  - G. Cristina Brailoiu
AU  - Eugen Brailoiu
AU  - Khalid Benamar
AU  - Mary E. Abood
TI  - The Lysophosphatidylinositol Receptor GPR55 Modulates Pain Perception in the Periaqueductal Gray
AID  - 10.1124/mol.115.099333
DP  - 2015 Aug 01
TA  - Molecular Pharmacology
PG  - 265--272
VI  - 88
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/88/2/265.short
4100  - http://molpharm.aspetjournals.org/content/88/2/265.full
SO  - Mol Pharmacol2015 Aug 01; 88
AB  - Emerging evidence indicates the involvement of GPR55 and its proposed endogenous ligand, lysophosphatidylinositol (LPI), in nociception, yet their role in central pain processing has not been explored. Using Ca2+ imaging, we show here that LPI elicits concentration-dependent and GPR55-mediated increases in intracellular Ca2+ levels in dissociated rat periaqueductal gray (PAG) neurons, which express GPR55 mRNA. This effect is mediated by Ca2+ release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate receptors and by Ca2+ entry via P/Q-type of voltage-gated Ca2+ channels. Moreover, LPI depolarizes PAG neurons and upon intra-PAG microinjection, reduces nociceptive threshold in the hot-plate test. Both these effects are dependent on GPR55 activation, because they are abolished by pretreatment with ML-193 [N-(4-(N-(3,4-dimethylisoxazol-5-yl)sulfamoyl)-phenyl)-6,8-dimethyl-2-(pyridin-2-yl)quinoline-4-carboxamide], a selective GPR55 antagonist. Thus, we provide the first pharmacological evidence that GPR55 activation at central levels is pronociceptive, suggesting that interfering with GPR55 signaling in the PAG may promote analgesia.