Details

Autor(en) / Beteiligte

• Smith, Jacqueline A. M.
• Davis, Clare L.
• Burgess, Gillian M.

Titel

Prostaglandin E 2 ‐induced sensitization of bradykinin‐evoked responses in rat dorsal root ganglion neurons is mediated by cAMP‐dependent protein kinase A

Ist Teil von

• The European journal of neuroscience, 2000-09, Vol.12 (9), p.3250-3258

Erscheinungsjahr

2000

Link zum Volltext

Quelle

Psychology & Behavioral Sciences Collection

Beschreibungen/Notizen

• Abstract Primary cultures of neonatal rat dorsal root ganglion (DRG) neurons were used to examine the mechanisms underlying both the direct activation and the sensitization of sensory neurons by prostanoids. Prostaglandin E 2 (PGE 2 ) elevated cytosolic calcium concentration ([Ca 2+ ] i ) in a subpopulation of small (< 19 μm) diameter, capsaicin‐sensitive DRG neurons. PGE 2 also stimulated substance P (SP) release from DRG cultures. In contrast to bradykinin, PGE 2 did not stimulate phosphoinositidase C (PIC) and the PGE 2 ‐evoked increase in [Ca 2+ ] i was dependent on extracellular calcium. Pre‐treatment with PGE 2 potentiated bradykinin‐evoked increases in [Ca 2+ ] i in small diameter neurons and increased the number of cells that responded to low concentrations of bradykinin. A similar effect was seen with prostaglandin I 2 (PGI 2 ) but not prostaglandin F 2α (PGF 2α ). PGE 2 pretreatment also potentiated bradykinin‐evoked release of SP, inducing a leftward shift in the bradykinin concentration–response curve and an increase in the maximum response. PGE 2 stimulated adenylyl cyclase activity in DRG cultures, at concentrations and times consistent with those required to observe both the direct and sensitizing effects of the prostanoid on [Ca 2+ ] i responses. Furthermore, the direct and sensitizing effects of PGE 2 , on both [Ca 2+ ] i responses and SP release, were mimicked by the membrane permeant cAMP analogue dibutyryl cAMP and inhibited by H89, an inhibitor of cAMP‐dependent protein kinase A (PKA). These observations are consistent with the hypothesis that both direct activation and sensitization of sensory neurons by prostanoids, such as PGE 2 , are mediated by PKA‐dependent phosphorylation mechanisms.