title: Beta3-adrenoceptors in the rat sacral spinal cord and their functional relevance in micturition under normal conditions and in a model of partial urethral obstruction.
abstract: OBJECTIVE
  Beta3-adrenoceptor selective agonists are evaluated as a new treatment for patients with lower urinary tract symptoms . It is believed that β3-AR selective agonists exert their effects via a peripheral site of action. However, β3-ARs have been found in brain tissue. This study examined whether β3-ARs are present in rat sacral spinal cord, and whether there are differences in β3-AR expression between normal and partial urethral obstruction (PUO) animals, and furthermore assessed the functional relevance of spinal β3-ARs for micturition.
  
  
  METHODS
  Thirty-eight male Sprague-Dawley rats underwent either PUO or sham-operation. Two weeks after operation, half of the animals were used for histomorphological analysis. Remaining animals were used for functional experiments, where a β3-AR selective agonist, BRL 37344, was given intrathecally. Bladder function was assessed by continuous cystometry in non-anesthetized animals before and after drug administration.
  
  
  RESULTS
  Beta3-ARs were found in sacral spinal cord segments with an accumulation in the ventral horn. There was a significant increase of β3-AR expression in obstructed rats. In functional experiments obstructed rats showed increased bladder weight, micturition frequency, spontaneous activity, and bladder pressures (all P < 0.05) compared to controls. Intrathecally administered BRL 37344 showed no effect in non-obstructed rats. In obstructed rats intrathecal BRL 37344 significantly reduced bladder pressures, spontaneous activity, and micturition frequency (all P < 0.05).
  
  
  CONCLUSIONS
  Beta3-ARs are present in rat sacral spinal cord, and are significantly up-regulated after PUO. Besides their well-established peripheral site of action in the treatment of voiding dysfunction, β3-AR selective agonists might exert relevant effects at a central nervous site of action.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University, Winston-Salem, NC, USA. claudius.fuellhase@med.uni-muenchen.de
authors.forename: Claudius
authors.initials: C
authors.lastname: Füllhase
authors.forename: Roberto
authors.initials: R
authors.lastname: Soler
authors.forename: Kristian
authors.initials: K
authors.lastname: Westerling-Andersson
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000008:administration & dosage; D007150:Immunohistochemistry; D008297:Male; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D012447:Sacrum; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation; D014524:Urethral Obstruction / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001743:Urinary Bladder / Q000294:innervation*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D004983:Ethanolamines; D022702:Receptors, Adrenergic, beta-3; C057368:BRL 37344