Biomaterial Database

The roles of muscarinic receptor subtypes in modulation of nasal ciliary action. 1996

B Yang, and T V McCaffrey

Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota, USA.

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.

UI	MeSH Term	Description	Entries
D009079	Mucociliary Clearance	A non-specific host defense mechanism that removes MUCUS and other material from the LUNGS by ciliary and secretory activity of the tracheobronchial submucosal glands. It is measured in vivo as mucus transfer, ciliary beat frequency, and clearance of radioactive tracers.	Mucociliary Transport,Clearance, Mucociliary,Clearances, Mucociliary,Mucociliary Clearances,Mucociliary Transports,Transport, Mucociliary,Transports, Mucociliary
D009297	Nasal Mucosa	The mucous lining of the NASAL CAVITY, including lining of the nostril (vestibule) and the OLFACTORY MUCOSA. Nasal mucosa consists of ciliated cells, GOBLET CELLS, brush cells, small granule cells, basal cells (STEM CELLS) and glands containing both mucous and serous cells.	Nasal Epithelium,Schneiderian Membrane,Epithelium, Nasal,Membrane, Schneiderian,Mucosa, Nasal
D010880	Piperidines	A family of hexahydropyridines.
D010890	Pirenzepine	An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.	Gastrotsepin,Gastrozepin,L-S 519,LS-519,Piren-Basan,Pirenzepin,Pirenzepin Von Ct,Pirenzepin-Ratiopharm,Pirenzepine Dihydrochloride,Pyrenzepine,Ulcoprotect,Ulgescum,Dihydrochloride, Pirenzepine,LS 519,LS519,Piren Basan,Pirenzepin Ratiopharm,Von Ct, Pirenzepin
D011976	Receptors, Muscarinic	One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.	Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D002923	Cilia	Populations of thin, motile processes found covering the surface of ciliates (CILIOPHORA) or the free surface of the cells making up ciliated EPITHELIUM. Each cilium arises from a basic granule in the superficial layer of CYTOPLASM. The movement of cilia propels ciliates through the liquid in which they live. The movement of cilia on a ciliated epithelium serves to propel a surface layer of mucus or fluid. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Motile Cilia,Motile Cilium,Nodal Cilia,Nodal Cilium,Primary Cilia,Primary Cilium,Cilium,Cilia, Motile,Cilia, Nodal,Cilia, Primary,Cilium, Motile,Cilium, Nodal,Cilium, Primary
D005703	Gallamine Triethiodide	A synthetic nondepolarizing blocking drug. The actions of gallamine triethiodide are similar to those of TUBOCURARINE, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. It should be used cautiously in patients at risk from increased heart rate but may be preferred for patients with bradycardia. (From AMA Drug Evaluations Annual, 1992, p198)	Gallamine,Gallamonium Iodide,Flaxedil,Gallamine Triethochloride,Gallamine Triethyl Iodide,Iodide, Gallamine Triethyl,Iodide, Gallamonium,Triethiodide, Gallamine,Triethochloride, Gallamine,Triethyl Iodide, Gallamine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001285	Atropine	An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.	AtroPen,Atropin Augenöl,Atropine Sulfate,Atropine Sulfate Anhydrous,Atropinol,Anhydrous, Atropine Sulfate,Augenöl, Atropin,Sulfate Anhydrous, Atropine,Sulfate, Atropine
D016210	Methacholine Chloride	A quaternary ammonium parasympathomimetic agent with the muscarinic actions of ACETYLCHOLINE. It is hydrolyzed by ACETYLCHOLINESTERASE at a considerably slower rate than ACETYLCHOLINE and is more resistant to hydrolysis by nonspecific CHOLINESTERASES so that its actions are more prolonged. It is used as a parasympathomimetic bronchoconstrictor agent and as a diagnostic aid for bronchial asthma. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1116)	Methacholine,2-(Acetyloxy)-N,N,N-trimethyl-1-propanaminium Chloride,Acetyl-2-methylcholine Chloride,Acetyl-beta-methacholine Chloride,Acetyl-beta-methylcholine,Mecholine,Mecholyl,Provocholine,Provokit,Acetyl 2 methylcholine Chloride,Acetyl beta methacholine Chloride,Acetyl beta methylcholine,Chloride, Methacholine