title: Is there a peripheral site of action contributing to the voiding effects of α₂-adrenoceptor agonists and antagonists?
abstract: OBJECTIVE
  Since it has not been established whether there is an effect on voiding exerted by direct stimulation or blockade of α2-adrenoceptors in the bladder and urethra, MK-467, a peripherally acting α2-adrenoceptor antagonist not penetrating into the CNS, was used to test whether part of the voiding effects of systemically given α2-adrenoceptor agonists is peripheral.
  
  
  METHODS
  Urodynamic recordings from 27 conscious male adult C57/Bl J-strain mice were performed. After vehicle (saline) administration, two groups of animals were treated first with the selective α2-adrenoceptor agonist dexmedetomidine (Dex) and then with the selective α2-adrenoceptor antagonists atipamezole (Ati) or MK-467. Two other groups were first treated with Ati or MK-467 and then with Dex.
  
  
  RESULTS
  Treatment with vehicle or α2-adrenoceptor antagonists alone did not affect micturition parameters. All animals treated first with Dex-developed overflow incontinence. Treatment with Ati after Dex reversed almost totally the effects of Dex on all voiding parameters, but treatment with MK-467 after Dex showed no detectable improvement. Treatment with Dex after Ati had no effect on any voiding parameter except maximal pressure. When mice were treated with Dex after MK-467, overflow incontinence was produced in seven of eight animals studied.
  
  
  CONCLUSIONS
  The absence of functionally relevant peripheral effects on voiding mediated via α2-adrenoceptors is supported by the finding that neither Ati nor MK-467 alone had any effect on micturition parameters and by the inability of MK-467 to inhibit the effects of Dex, suggesting that the relevant Dex effects were exerted within the CNS.
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Erik
authors.initials: E
authors.lastname: Aro
authors.forename: Sanna
authors.initials: S
authors.lastname: Bastman
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Tomi
authors.initials: T
authors.lastname: Streng
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010525:Peripheral Nerves / Q000187:drug effects* / Q000502:physiology; D011807:Quinolizines / Q000494:pharmacology; D014521:Urethra / Q000294:innervation / Q000502:physiology; D001743:Urinary Bladder / Q000294:innervation / Q000502:physiology; D014554:Urination / Q000187:drug effects* / Q000502:physiology; D014563:Urodynamics / Q000187:drug effects* / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D007093:Imidazoles; D011807:Quinolizines; C050701:atipamezole; C055732:vatinoxan; D020927:Dexmedetomidine