Abstract
Bradykinin (BK) and its receptors, B(1) and B(2), in trigeminal ganglion (TG) neurons are involved in the regulation of pain. Recent studies have revealed that B(1) receptors are expressed in neonatal rat TG neurons; however, the intracellular signaling pathway following B(1) receptor activation remains to be elucidated. To investigate the mechanism by which B(1) receptor activation leads to intracellular Ca(2+) mobilization, we measured the intracellular free Ca(2+) concentration ([Ca(2+)](i)) in primary-cultured TG neurons. The application of Lys-[Des-Arg(9)]BK (B(1) receptor agonist) increased the [Ca(2+)](i) in these TG neurons even in the absence of extracellular Ca(2+). Pretreatment with inhibitors of ryanodine receptors or sarco/endoplasmic reticulum Ca(2+)-ATPase suppressed the increase in Lys-[Des-Arg(9)]BK-induced [Ca(2+)](i). The Lys-[Des-Arg(9)]BK-induced [Ca(2+)](i) increase was unaffected by phospholipase-C inhibitor. B(1) receptor activation-induced [Ca(2+)](i) increase was suppressed by phosphodiesterase inhibitor and enhanced by adenylyl cyclase inhibitor. These results suggest that B(1) receptor activation suppresses intracellular cAMP production via adenylyl cyclase inhibition and mobilizes intracellular Ca(2+) via ryanodine receptors that access intracellular Ca(2+) stores.