title: Action of naftopidil on spinal serotonergic neurotransmission for inhibition of the micturition reflex in rats.
abstract: We examined the mechanism of action of naftopidil, an α1D/A blocker, on spinal descending serotonergic neurotransmission for the micturition reflex.
  
  
  
  We examined (1) urinary 5-hydroxyindole acetic acid (5-HIAA) after intraperitoneal administration of saline, para-chlorophenylalanine (PCPA; a serotonin synthetic enzyme inhibitor), and/or 5-hydroxytryptophan (5-HTP; a serotonin precursor); (2) isovolumetric cystometry after intraperitoneal administration of saline, PCPA, and/or 5-HTP and intravenous injection of naftopidil; and (3) isovolumetric cystometry before and after intrathecal administration of serotonin (5-HT) receptor antagonists and intravenous injection of naftopidil.
  
  
  
  PCPA decreased and 5-HTP increased urinary 5-HIAA/creatinine. Intraperitoneal injection of PCPA did not influence cystometric parameters. Intraperitoneal injection of 5-HTP significantly shortened the interval between bladder contractions. Intravenous injection of naftopidil transiently abolished bladder contractions. However, the duration of abolishment of bladder contractions after injection of naftopidil in rats given PCPA was significantly shorter than that in rats given vehicle, but significantly longer than that in rats given PCPA and 5-HTP. Intrathecal injection of 5-HT1B, 5-HT3, or 5-HT7 receptor antagonists significantly prolonged the interval between bladder contractions. Intrathecal injection of 5-HT1D or 5-HT2B receptor antagonists significantly shortened the interval between bladder contractions. Combined administration of the maximum non-effective dose of 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, or 5-HT3 receptor antagonists and intravenous injection of naftopidil significantly shortened the duration of abolishment of bladder contraction compared to intravenous injection of naftopidil alone.
  
  
  
  Naftopidil may inhibit the micturition reflex via 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT3 receptors in the spinal cord. Neurourol. Urodynam. 36:604-609, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Southern Knights' Laboratory, Okinawa, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Sugaya
authors.affiliation: Southern Knights' Laboratory, Okinawa, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Nishijima
authors.affiliation: Southern Knights' Laboratory, Okinawa, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kadekawa
authors.affiliation: Southern Knights' Laboratory, Okinawa, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ashitomi
authors.affiliation: Faculty of Medicine, Institute for Animal Experiments, 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
authors.affiliation: Department of Medical Affairs, Asahi Kasei Pharma Corporation, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hattori
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D009281:Naphthalenes / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D014554:Urination / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D009281:Naphthalenes; D010879:Piperazines; D012702:Serotonin Antagonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D010134:Fenclonine; C064357:naftopidil
keywords: 5-HT; naftopidil; serotonin; spinal cord