title: M1 and M3 muscarinic receptors mediate relaxation and contraction in canine nasal veins.
abstract: BACKGROUND
  Acetylcholine (ACh) has been shown to induce nasal congestion via vasorelaxation of intranasal posterior collecting veins (PCV) coupled with vasocontraction of extranasal outflow veins (dorsal nasal vein [DNV] and sphenopalatine vein [SPV]). The aim of this study was to characterize the muscarinic receptor subtype(s) involved in ACh-induced relaxation and contraction in canine nasal veins.
  
  
  METHODS
  PCV, DNV, and SPV were isolated from the canine nose. In vitro isometric tension of segments from these veins was monitored to reflect vascular reactivity. ACh concentration-response curve was studied in the presence of muscarinic receptor subtype inhibitors. Immunohistochemical localization of M(1)-M(5) receptor subtypes in the veins was performed.
  
  
  RESULTS
  ACh-induced relaxation in PVC was inhibited by pertussis toxin (PTX; inhibitor of G-protein that couples M(2)/M(4) receptors), methoctramine (selective M(2) muscarinic receptor inhibitor), muscarinic toxin 7 (MT-7; selective M(1) muscarinic receptor inhibitor), and 4-diphenylacetoxy-methylpiperidine methiodide (4-DAMP; selective M(3) muscarinic receptor inhibitor). ACh-induced contraction in SPV and DNV was potentiated by PTX and methoctramine but was inhibited by MT-7 and 4-DAMP. Immunohistochemistry confirmed the presence of five muscarinic receptor subtypes in the endothelium of nasal veins, with staining of M(3) > M(1) > M(5) > M(2) = M(4) in PVC but M(2) = M(4) > M(3) > M(1) > M(5) in outflow veins. M(1) and M(3) receptor subtypes were localized in the smooth muscles of both types of veins.
  
  
  CONCLUSIONS
  The results show that ACh relaxes intranasal veins and contracts extranasal veins primarily via M(1) and M(3) muscarinic receptor subtypes, implying the therapeutic value of M(1)/M(3)-specific or highly selective anticholinergics on nasal congestion.
authors.affiliation: Department of Physiology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, China. makylung@hkucc.hku.hk
authors.forename: Mary A
authors.initials: MA
authors.lastname: Lung
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003959:Diamines / Q000494:pharmacology; D004285:Dogs; D004546:Elapid Venoms / Q000494:pharmacology; D015508:Nasal Obstruction / Q000188:drug therapy*; D009666:Nose / Q000473:pathology; D037342:Pertussis Toxin / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014680:Veins / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D003959:Diamines; D004546:Elapid Venoms; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; C419876:muscarinic toxin 7; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D037342:Pertussis Toxin; D000109:Acetylcholine; C054938:methoctramine