Intracellular Ca2+mobilization pathway via bradykinin B1receptor activation in rat trigeminal ganglion neurons

Bradykinin (BK) and its receptors, B1and B2, in trigeminal ganglion (TG) neurons are involved in the regulation of pain. Recent studies have revealed that B1receptors are expressed in neonatal rat TG neurons; however, the intracellular signaling pathway following B1receptor activation remains to be elucidated. To investigate the mechanism by which B1receptor 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 (B1receptor agonist) increased the [Ca2+]iin 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+]iincrease was unaffected by phospholipase-C inhibitor. B1receptor activation-induced [Ca2+]iincrease was suppressed by phosphodiesterase inhibitor and enhanced by adenylyl cyclase inhibitor. These results suggest that B1receptor activation suppresses intracellular cAMP production via adenylyl cyclase inhibition and mobilizes intracellular Ca2+via ryanodine receptors that access intracellular Ca2+stores.