Intracellular Ca 2+ mobilization pathway via bradykinin B 1 receptor activation in rat trigeminal ganglion neurons

Abstract

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.

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