@article {Deliumol.115.099333, author = {Elena Deliu and Margaret Sperow and Linda Console-Bram and Rhonda L Carter and Douglas G Tilley and Daniel J Kalamarides and Lynn G Kirby and G. Cristina Brailoiu and Eugen Brailoiu and Khalid Benamar and Mary E. Abood}, title = {The Lysophosphatidylinositol Receptor GPR55 Modulates Pain Perception in the Periaqueduactal Grey}, elocation-id = {mol.115.099333}, year = {2015}, doi = {10.1124/mol.115.099333}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Emerging evidence indicates the involvement of GPR55 and its proposed endogenous ligand, lysophosphatidylinositol (LPI), in nociception, yet their role at 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, since they are abolished by pretreatment with ML-193, 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.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/early/2015/05/12/mol.115.099333}, eprint = {https://molpharm.aspetjournals.org/content/early/2015/05/12/mol.115.099333.full.pdf}, journal = {Molecular Pharmacology} }