The Lysophosphatidylinositol Receptor GPR55 Modulates Pain Perception in the Periaqueductal Gray.

Abstract

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 Ca(2+) imaging, we show here that LPI elicits concentration-dependent and GPR55-mediated increases in intracellular Ca(2+) levels in dissociated rat periaqueductal gray (PAG) neurons, which express GPR55 mRNA. This effect is mediated by Ca(2+) release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate receptors and by Ca(2+) entry via P/Q-type of voltage-gated Ca(2+) 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.

• Authors: Elena Deliu, Margaret Sperow, Linda Console-Bram, Rhonda L Carter, Douglas G Tilley, Daniel J Kalamarides, Lynn G Kirby, G Cristina Brailoiu, Eugen Brailoiu, Khalid Benamar, Mary E Abood
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 88 Issue 2 Pg. 265-72 (Aug 2015) ISSN: 1521-0111 [Electronic] United States
• PMID: 25972448 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Chemical References

• GPR55 protein, mouse
• Lysophospholipids
• Receptors, Cannabinoid
• lysophosphatidylinositol
• Calcium

Topics

• Animals
• Animals, Newborn
• Calcium (metabolism)
• Cells, Cultured
• Female
• Lysophospholipids (pharmacology)
• Male
• Membrane Potentials (drug effects)
• Neurons (physiology)
• Pain Perception
• Periaqueductal Gray (physiology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Cannabinoid (genetics, metabolism)