OBJECTIVES: Adrenergic alpha(1)-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 alpha(1)-adrenoceptors involved in these effects are not known. METHODS: We have studied in the rat whether functional alpha(1)-adrenoreceptors are expressed in primary sensory neurons, and whether they regulate neurogenic inflammation and nociceptive responses in the urinary bladder. RESULTS: The alpha(1)-adrenoreceptor agonist phenylephrine (1 micromol/l) (1) mobilized intracellular Ca(2+) 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 alpha(1)-adrenoceptor antagonist alfuzosin (10 micromol/l). Furthermore, alfuzosin (30 microg/kg, i.v.) partially, but significantly, inhibited cyclophosphamide-induced plasma protein extravasation in the rat urinary bladder. Phenylephrine-induced Ca(2+) 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. CONCLUSIONS: Alpha(1)-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 alpha(1)-adrenoceptor antagonists in the amelioration of storage symptoms in the lower urinary tract derives from their inhibitory effect on neurogenic inflammatory responses.
OBJECTIVES: Adrenergic alpha(1)-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 alpha(1)-adrenoceptors involved in these effects are not known. METHODS: We have studied in the rat whether functional alpha(1)-adrenoreceptors are expressed in primary sensory neurons, and whether they regulate neurogenic inflammation and nociceptive responses in the urinary bladder. RESULTS: The alpha(1)-adrenoreceptor agonist phenylephrine (1 micromol/l) (1) mobilized intracellular Ca(2+) 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 alpha(1)-adrenoceptor antagonist alfuzosin (10 micromol/l). Furthermore, alfuzosin (30 microg/kg, i.v.) partially, but significantly, inhibited cyclophosphamide-induced plasma protein extravasation in the rat urinary bladder. Phenylephrine-induced Ca(2+) 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. CONCLUSIONS: Alpha(1)-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 alpha(1)-adrenoceptor antagonists in the amelioration of storage symptoms in the lower urinary tract derives from their inhibitory effect on neurogenic inflammatory responses.
Authors: Anna P Malykhina; Jean-Jacques Wyndaele; Karl-Erik Andersson; Stefan De Wachter; Roger R Dmochowski Journal: Neurourol Urodyn Date: 2012-02-29 Impact factor: 2.696
Authors: Rita Matos; Paula Serrão; Larissa Rodriguez; Lori Ann Birder; Francisco Cruz; Ana Charrua Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2017-05-31 Impact factor: 3.000
Authors: S Palea; A Maiga; V Guilloteau; M Rekik; M Guérard; C Rouget; P Rischmann; H Botto; P Camparo; P Lluel; N Gilles Journal: Br J Pharmacol Date: 2013-02 Impact factor: 8.739
Authors: Pascale S Guiton; Thomas J Hannan; Bradley Ford; Michael G Caparon; Scott J Hultgren Journal: Infect Immun Date: 2012-11-06 Impact factor: 3.441