Angiotensin II type 2 receptor (AT2 R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons.

摘要: Background: The angiotensin II (AngII) receptor subtype 2 (AT2R) is expressed in sensory neurons and may play a role nociception neuronal regeneration. Methods: We used immunostaining with characterized antibodies to study the localization of AT2R cultured human rat dorsal root ganglion (DRG) range tissues. effects AngII antagonist EMA401 on capsaicin responses were measured calcium imaging, neurite length density Gap43 immunostaining, cyclic adenosine monophosphate (cAMP) expression using immunofluorescence. Results: was localized small-/medium-sized DRG. Treatment resulted dose-related functional inhibition (IC50 = 10 nmol/L), which reversed by 8-bromo-cAMP, reduced density; treatment significantly enhanced responses, cAMP levels outgrowth. AT1R losartan had no effect responses. sensoryneuronsofhumanDRG,andnervefibresinperipheralnerves,skin, urinary bladder bowel. A majority sub-population (60%) small-/ medium-diameter cells immunopositive both control post-mortem avulsion-injured DRG; some very small appeared be intensely immunoreactive, TRPV1 co-localization. While limb peripheral nerve segments proximal injury, they preserved painful neuromas. Conclusions: antagonists could particularly useful chronic pain hypersensitivity associated abnormal sprouting.