title: Spinal mechanism of micturition reflex inhibition by naftopidil in rats.
abstract: OBJECTIVE
  We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats.
  
  
  METHODS
  The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions.
  
  
  RESULTS
  Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1mg) or IT (0.1μg) noradrenaline evoked bladder contractions, but IV (1mg) or IT (0.01-1μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions.
  
  
  CONCLUSIONS
  Naftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system.
authors.affiliation: Southern Knights' Laboratory LLP, Okinawa, Japan. Electronic address: sugaya@sklabo.com.
authors.forename: Kimio
authors.initials: K
authors.lastname: Sugaya
authors.affiliation: Southern Knights' Laboratory LLP, Okinawa, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Nishijima
authors.affiliation: Southern Knights' Laboratory LLP, Okinawa, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kadekawa
authors.affiliation: Southern Knights' Laboratory LLP, Okinawa, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ashitomi
authors.affiliation: The Institute for Animal Experiments, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005998:Glycine / Q000378:metabolism; D007278:Injections, Spinal; D009119:Muscle Contraction / Q000187:drug effects*; D009281:Naphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013331:Strychnine / Q000494:pharmacology; D014018:Tissue Distribution; D014554:Urination / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D000596:Amino Acids; D009281:Naphthalenes; D010879:Piperazines; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D013331:Strychnine; C064357:naftopidil; D005998:Glycine; D009638:Norepinephrine; D001640:Bicuculline
keywords: Bicuculline; Micturition reflex; Naftopidil; Noradrenaline; Strychnine