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Bupivacaine inhibits endothelin-1 evoked increases in intracellular calcium in model sensory neurons
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2014 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Background: Endothelin-1 (ET-1) induces pain and sensitization by activating the Gq protein-coupled receptor endothelin-A (ETA). Activation of ETA receptors on nociceptors membrane evokes intracellular calcium transients and excites the neurons, which presumably underlie ET-1’s pro-nociceptive effects in vivo. Local anesthetics inhibit the Gqprotein-coupled signaling of several inflammatory and pain modulating mediators. In this study, we aimed to investigate the actions of local anesthetics on the ETA-mediated increases in intracellular calcium in ND7/104 sensory neurons.

Methods: Increases in intracellular calcium were measured by the fluorescent indicator fura-2-AM loaded in a sensory neuron-derived cell line (ND7/104) expressing ETA receptors. Cells were pre-incubated with local anesthetic before ET-1 exposure and peak amplitudes were measured. 

Results: Bupivacaine suppressed ET-1 responses in a concentration-dependent and non-competitive manner with an IC50of 3.79 + 1.63 mM. Bupivacaine at 6 mM reduced Emax for ET-1 from 50.07 (95% CI 46.08 – 54.06) to 27.30 (95% CI 21.11 – 33.49). The actions of bupivacaine occurred quickly and were rapidly reversible. In contrast, 10 mM lidocaine and 10 mM QX-314, separately, had no effect.

Conclusion: Bupivacaine inhibits ETA-mediated calcium transients at clinically achieved concentrations. This suggests that some of bupivacaine’s beneficial effects might be due to an interaction with ET-1 signaling.

Place, publisher, year, edition, pages
2014. , 54 p.
Keyword [en]
"Endothelin-1" "local anesthetics" "G protein-coupled receptor" "endothelin-A receptor" "model sensory neurons" "calcium"
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-217190OAI: oai:DiVA.org:uu-217190DiVA: diva2:692499
External cooperation
Harvard Medical School
Subject / course
Pharmaceutical Biosciences
Educational program
Master of Science Programme in Pharmacy
Available from: 2014-06-03 Created: 2014-01-31 Last updated: 2014-06-03Bibliographically approved

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