Intracellular Ca2+ mobilization pathway via bradykinin B1 receptor activation in rat trigeminal ganglion neurons
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Bradykinin (BK) and its receptors, B1 and B2, in trigeminal ganglion (TG) neurons are involved in the regulation of pain. Recent studies have revealed that B1 receptors are expressed in neonatal rat TG neurons; however, the intracellular signaling pathway following B1 receptor activation remains to be elucidated. To investigate the mechanism by which B1 receptor activation leads to intracellular Ca2+ mobilization, we measured the intracellular free Ca2+ concentration ([Ca2+]i) in primary-cultured TG neurons. The application of Lys-[Des-Arg9]BK (B1 receptor agonist) increased the [Ca2+]i in these TG neurons even in the absence of extracellular Ca2+. Pretreatment with inhibitors of ryanodine receptors or sarco/endoplasmic reticulum Ca2+-ATPase suppressed the increase in Lys-[Des-Arg9]BK-induced [Ca2+]i. The Lys-[Des-Arg9]BK-induced [Ca2+]i increase was unaffected by phospholipase-C inhibitor. B1 receptor activation-induced [Ca2+]i increase was suppressed by phosphodiesterase inhibitor and enhanced by adenylyl cyclase inhibitor. These results suggest that B1 receptor activation suppresses intracellular cAMP production via adenylyl cyclase inhibition and mobilizes intracellular Ca2+ via ryanodine receptors that access intracellular Ca2+ stores.
KeywordsAdenylyl cyclase Ca2+ mobilization Cyclic AMP G protein Ryanodine receptors Trigeminal ganglion neuron
The authors thank the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) and the Multidisciplinary Research Center for Jaw Disease (MRCJD) for financial support.
RT, MK, TI, MT and YS were responsible for the conception and design of the experiments. RT, MK, AH, YK and YS were responsible for the acquisition, analysis and interpretation of data. RT, MK, TI, MT and YS were responsible for drafting and critically revising the intellectual content of the article. YS was responsible for final approval of the version to be submitted/published; All authors have read and approved the final manuscript.
This research was funded by JSPS KAKENHI (grant numbers JP15K11129, JP15K11056) and by Multidisciplinary Research Center for Jaw Disease (MRCJD): Achieving Longevity and Sustainability by Comprehensive Reconstruction of Oral and Maxillofacial Functions
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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