M1and M3Muscarinic Receptors Mediate Relaxation and Contraction in Canine Nasal Veins
Copyright policy )M1and M3Muscarinic Receptors Mediate Relaxation and Contraction in Canine Nasal Veins
BackgroundAcetylcholine (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.MethodsPCV, 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 M1–M5receptor subtypes in the veins was performed.ResultsACh-induced relaxation in PVC was inhibited by pertussis toxin (PTX; inhibitor of G-protein that couples M2/M4receptors), methoctramine (selective M2muscarinic receptor inhibitor), muscarinic toxin 7 (MT-7; selective M1muscarinic receptor inhibitor), and 4-diphenylacetoxy-methylpiperidine methiodide (4-DAMP; selective M3muscarinic 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 M3> M1> M5> M2= M4in PVC but M2= M4> M3> M1> M5in outflow veins. M1and M3receptor subtypes were localized in the smooth muscles of both types of veins.ConclusionThe results show that ACh relaxes intranasal veins and contracts extranasal veins primarily via M1and M3muscarinic receptor subtypes, implying the therapeutic value of M1/M3-specific or highly selective anticholinergics on nasal congestion.
- University of Hong Kong China (People's Republic of)
- University of Hong Kong (香港大學) China (People's Republic of)
Acetylcholine - pharmacology, Muscarinic M1 - antagonists and inhibitors - metabolism, Diamines, Nose, Receptor, Muscarinic M1 - antagonists and inhibitors - metabolism, Veins, Receptor, Muscarinic M3 - antagonists and inhibitors - metabolism, Dogs, Piperidines, 616, Animals, Cells, Cultured, Elapid Venoms, Receptor, Muscarinic M3, Receptor, Muscarinic M1, Acetylcholine, Vasodilation, Pertussis Toxin, Vasoconstriction, Muscarinic M3 - antagonists and inhibitors - metabolism, Nasal Obstruction, Veins - drug effects - metabolism - pathology, Nasal Obstruction - drug therapy, Receptor
Acetylcholine - pharmacology, Muscarinic M1 - antagonists and inhibitors - metabolism, Diamines, Nose, Receptor, Muscarinic M1 - antagonists and inhibitors - metabolism, Veins, Receptor, Muscarinic M3 - antagonists and inhibitors - metabolism, Dogs, Piperidines, 616, Animals, Cells, Cultured, Elapid Venoms, Receptor, Muscarinic M3, Receptor, Muscarinic M1, Acetylcholine, Vasodilation, Pertussis Toxin, Vasoconstriction, Muscarinic M3 - antagonists and inhibitors - metabolism, Nasal Obstruction, Veins - drug effects - metabolism - pathology, Nasal Obstruction - drug therapy, Receptor
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