title: Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries.
abstract: OBJECTIVE
  5-HT is taken up by and stored in adrenergic nerves and periarterial nerve stimulation (PNS) releases 5-HT to cause vasoconstriction in rat mesenteric arteries. The present study investigated whether PNS-released 5-HT stored in adrenergic nerves affects the function of perivascular calcitonin gene-related peptide-containing (CGRPergic) nerves.
  
  
  METHODS
  Rat mesenteric vascular beds without endothelium and with active tone were perfused with Krebs solution. Changes in perfusion pressure in response to PNS and CGRP injection were measured before (control) and after perfusion of Krebs solution containing 5-HT (10 µM) for 20 min. Distributions of 5-HT- and TH-immunopositive fibres in mesenteric arteries were studied using immunohistochemical methods.
  
  
  RESULTS
  PNS (1-4 Hz) frequency dependently caused adrenergic nerve-mediated vasoconstriction followed by CGRPergic nerve-mediated vasodilatation. 5-HT treatment inhibited PNS-induced vasodilatation without affecting exogenous CGRP-induced vasodilatation, while it augmented PNS-induced vasoconstriction. Guanethidine (adrenergic neuron blocker), methysergide (non-selective 5-HT receptor antagonist) and BRL15572 (selective 5-HT1D receptor antagonist) abolished inhibition of PNS-induced vasodilatation in 5-HT-treated preparations. Combined treatment with 5-HT and desipramine (catecholamine transporter inhibitor), but not fluoxetine (selective 5-HT reuptake inhibitor), did not inhibit PNS-induced vasodilatation. Exogenous 5-HT inhibited PNS-induced vasodilatation, which was antagonized by methysergide. In immunohistochemical experiments, 5-HT-immunopositive nerves, colocalized with adrenergic TH-immunopositive nerves, were observed only in 5-HT-treated mesenteric arteries, but not in control preparations or arteries co-treated with desipramine.
  
  
  CONCLUSIONS
  These results suggest that 5-HT can be taken up by and released from adrenergic nerves in vitro by PNS to inhibit CGRPergic nerve transmission in rat mesenteric arteries.
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Fujii
authors.forename: Shingo
authors.initials: S
authors.lastname: Takatori
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Zamami
authors.forename: Narumi
authors.initials: N
authors.lastname: Hashikawa-Hobara
authors.forename: Natsuki
authors.initials: N
authors.lastname: Miyake
authors.forename: Panot
authors.initials: P
authors.lastname: Tangsucharit
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Mio
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D059331:Adrenergic Neurons / Q000502:physiology*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D003891:Desipramine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008729:Methoxamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D015740:Calcitonin Gene-Related Peptide; D003891:Desipramine; D005473:Fluoxetine; D006145:Guanethidine; D008729:Methoxamine; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors