The roles of muscarinic receptor subtypes in modulation of nasal ciliary action.
Muscarinic receptors are believed to play an important role in modulation of ciliary action in respiratory system. We studied the in vitro effect of methacholine, a beta-methyl ester of acetylcholine, on the ciliary beat frequency (CBF). Adenoid explants were cultured in Minimum Essential Medium Eagle (MEM). CBF was determined using microphotometry. Methacholine (10(-6) M) increased CBF a maximum of 10.34 +/- 0.42% (p < 0.001). The non-selective muscarinic antagonist atropine (10(-6) M) significantly inhibited the ciliostimulatory effects of methacholine (p < 0.001). To characterize the muscarinic receptor subtypes in nasal mucosa, the selective M1-, M2- and M3-muscarinic antagonists pirenzepine dihydrochloride (PZ), gallamine triethiodide (gallamine), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) were used prior to addition of methacholine, PZ and 4-DAMP, at concentrations of 10(-6) to 10(-8) M, significantly inhibited the ciliostimulatory effects of methacholine (p < 0.0001). There was no significant inhibition of methacholine-induced ciliostimulation by gallamine (p > 0.3). Our study showed that ciliostimulation by methacholine in human upper airway mucosa involves M1- and M3- muscarinic receptor subtypes, but not the M2-receptor subtype. The identification of the muscarinic receptor subtypes and intracellular signalling mechanisms involved in CBF modulation will permit the selection appropriate of pharmacological agents for treating the cholinergic symptoms of rhinitis.
Yang
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B
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota, USA.
McCaffrey
T V
TV
D001285:Atropine / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology; D009079:Mucociliary Clearance / Q000502:physiology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009297:Nasal Mucosa / Q000737:chemistry / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D005703:Gallamine Triethiodide