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Robin Hodges, Dayu Li, Richard Carozza, Marie Shatos, Nan Chiang, Charles Serhan, Darlene Dartt; Resolvin D1 Receptor Activation Counter-regulates H1 histamine receptors in human and rat conjunctival goblet cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2114. doi: https://doi.org/.
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To determine the interactions between H1 histamine receptor (H1R) and GPR32, a GPCR receptor for the proresolution mediator, resolvin D1 (RvD1).
Rat conjunctival goblet cells were grown in culture. Chinese hamster ovary (CHO) cells were transfected with human H1R and GPR32 receptor. Intracellular [Ca2+] ([Ca2+]i) was measured in cells loaded with the calcium indicator dye fura 2.
In rat goblet cells, the H1R agonist histamine dimaleate significantly increased [Ca2+]i by 327.2 ± 71.5 nM. Exposure to RvD1 significantly inhibited this response to 92.6 ± 21.5 nM. The protein kinase C inhibitor Ro-317549 and an inhibitory peptide of β adrenergic receptor kinase 1 (βARK1) reversed the inhibition of RvD1 on the histamine dimaleate stimulated increase in [Ca2+]i to 197.2 ± 46.3 and 352.7 ± 89.6 nM, respectively. Similar results were obtained in CHO cells transfected with human H1R and human GPR32 receptor.
We conclude that RvD1 uses PKC and βARK1 to counter-regulate the H1R and inhibit its actions.
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