Abstract
ObjectivesAdrenergic α1-receptors agonists and antagonists have been reported to increase and reduce, respectively, neurogenic inflammatory responses mediated by capsaicin-sensitive sensory neurons. However, the precise role and localization of the α1-adrenoceptors involved in these effects are not known. MethodsWe have studied in the rat whether functional α1-adrenoreceptors are expressed in primary sensory neurons, and whether they regulate neurogenic inflammation and nociceptive responses in the urinary bladder. ResultsThe α1-adrenoreceptor agonist phenylephrine (1μmol/l) (1) mobilized intracellular Ca2+ in cultured lumbar and sacral dorsal root ganglia neurons, (2) caused the release of substance P (SP) from terminals of capsaicin-sensitive sensory neurons from the lumbar enlargement of the dorsal spinal cord and urinary bladder, and (3) increased plasma protein extravasation in the urinary bladder. All these effects were abolished by the α1-adrenoceptor antagonist alfuzosin (10μmol/l). Furthermore, alfuzosin (30μg/kg, iv) partially, but significantly, inhibited cyclophosphamide-induced plasma protein extravasation in the rat urinary bladder. Phenylephrine-induced Ca2+ mobilization in cultured dorsal root ganglia neurons was exaggerated by pretreating the rats in vivo with cyclophosphamide. Finally, cyclophosphamide increased c-fos expression in the rat lumbar spinal cord. Also these in vitro and in vivo effects were inhibited by pretreatment with alfuzosin. Conclusionsα1-Adrenoceptors are functionally expressed by capsaicin-sensitive, nociceptive, primary sensory neurons of the rat urinary tract, and their activation may contribute to signal irritative and nociceptive responses arising from the urinary tract. It is possible that, at least, part of the beneficial effects of α1-adrenoceptor antagonists in the amelioration of storage symptoms in the lower urinary tract derives from their inhibitory effect on neurogenic inflammatory responses.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have