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Article: On muscarinic control of neurogenic mucus secretion in ferret trachea

TitleOn muscarinic control of neurogenic mucus secretion in ferret trachea
Authors
Issue Date1996
PublisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0022-3751
Citation
Journal Of Physiology, 1996, v. 494 n. 2, p. 577-586 How to Cite?
Abstract1. Muscarinic receptor subtypes mediating neurogenic mucus secretion in ferret trachea were characterized in vitro and in vivo using 35SO4 as a label for secreted mucus, and the muscarinic receptor antagonists telenzepine for the M1 receptor subtype, methoctramine for the M2 subtype and 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) for the M3 receptor. We also performed receptor binding and mapping studies. 2. Each muscarinic antagonist displaced [N-methyl-3H]scopolamine binding with high=affinity binding constant (K(H)) values of 1.9, 2.7 and 5.0 nm for telenzepine, methoctramine and 4-DAMP, respectively. Muscarinic M1 and M3 receptors localized to submucosal glands, whereas M2 receptors did not. 3. In vitro, electrical stimulation (50 V, 10 Hz, 0.5ms for 5 min) increased 35SO4 output by 160%. Telenzepine did not inhibit the neurogenic secretory response at concentrations two- or twentyfold its K(H) value, nor did it inhibit secretion induced by acetylcholine (ACh). 4-DAMP inhibited neurogenic secretion by 80% and 95%, respectively, at concentrations two- and twentyfold its K(H) value, and also limited ACh-induced secretion. Methoctramine potentiated neurogenic secretion induced at 2.5 Hz (50 V, 0.5 ms for 5 min) in a dose-related (5.4-100 nM) manner with increases of 35-451% above electrically stimulated values. Methoctramine did not potentiate secretion induced at 10 Hz and did not have any effect on ACh-induced secretion. 4. In vivo, vagal stimulation(10 V, 10 Hz, 2 ms for 8 min) increased output of 35SO4 by ~120%. telenzepine had no significant effect on neurogenic secretion. Methoctramine approximately doubled the stimulated response, whereas 4-DAMP abolished the stimulated secretory response. 5. We conclude that in ferret trachea, cholinergic nerve stimulation increases mucus secretion via muscarinic M3 receptors on the submucosal glands. The magnitude of the secretory response is regulated by neuronal M2 muscarinic receptors. The muscarinic M1 receptors localized to the submucosal glands do not appear to be involved with mucus secretion.
Persistent Identifierhttp://hdl.handle.net/10722/162125
ISSN
2015 Impact Factor: 4.731
2015 SCImago Journal Rankings: 2.670
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRamnarine, SIen_US
dc.contributor.authorHaddad, EBen_US
dc.contributor.authorKhawaja, AMen_US
dc.contributor.authorMak, JCWen_US
dc.contributor.authorRogers, DFen_US
dc.date.accessioned2012-09-05T05:17:29Z-
dc.date.available2012-09-05T05:17:29Z-
dc.date.issued1996en_US
dc.identifier.citationJournal Of Physiology, 1996, v. 494 n. 2, p. 577-586en_US
dc.identifier.issn0022-3751en_US
dc.identifier.urihttp://hdl.handle.net/10722/162125-
dc.description.abstract1. Muscarinic receptor subtypes mediating neurogenic mucus secretion in ferret trachea were characterized in vitro and in vivo using 35SO4 as a label for secreted mucus, and the muscarinic receptor antagonists telenzepine for the M1 receptor subtype, methoctramine for the M2 subtype and 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) for the M3 receptor. We also performed receptor binding and mapping studies. 2. Each muscarinic antagonist displaced [N-methyl-3H]scopolamine binding with high=affinity binding constant (K(H)) values of 1.9, 2.7 and 5.0 nm for telenzepine, methoctramine and 4-DAMP, respectively. Muscarinic M1 and M3 receptors localized to submucosal glands, whereas M2 receptors did not. 3. In vitro, electrical stimulation (50 V, 10 Hz, 0.5ms for 5 min) increased 35SO4 output by 160%. Telenzepine did not inhibit the neurogenic secretory response at concentrations two- or twentyfold its K(H) value, nor did it inhibit secretion induced by acetylcholine (ACh). 4-DAMP inhibited neurogenic secretion by 80% and 95%, respectively, at concentrations two- and twentyfold its K(H) value, and also limited ACh-induced secretion. Methoctramine potentiated neurogenic secretion induced at 2.5 Hz (50 V, 0.5 ms for 5 min) in a dose-related (5.4-100 nM) manner with increases of 35-451% above electrically stimulated values. Methoctramine did not potentiate secretion induced at 10 Hz and did not have any effect on ACh-induced secretion. 4. In vivo, vagal stimulation(10 V, 10 Hz, 2 ms for 8 min) increased output of 35SO4 by ~120%. telenzepine had no significant effect on neurogenic secretion. Methoctramine approximately doubled the stimulated response, whereas 4-DAMP abolished the stimulated secretory response. 5. We conclude that in ferret trachea, cholinergic nerve stimulation increases mucus secretion via muscarinic M3 receptors on the submucosal glands. The magnitude of the secretory response is regulated by neuronal M2 muscarinic receptors. The muscarinic M1 receptors localized to the submucosal glands do not appear to be involved with mucus secretion.en_US
dc.languageengen_US
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0022-3751en_US
dc.relation.ispartofJournal of Physiologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshDiamines - Pharmacologyen_US
dc.subject.meshElectric Stimulationen_US
dc.subject.meshFerretsen_US
dc.subject.meshMaleen_US
dc.subject.meshMucus - Secretionen_US
dc.subject.meshMuscarinic Antagonists - Pharmacologyen_US
dc.subject.meshMuscle, Smooth - Drug Effects - Innervation - Physiologyen_US
dc.subject.meshPiperidines - Pharmacologyen_US
dc.subject.meshPirenzepine - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshQuinuclidinyl Benzilate - Metabolismen_US
dc.subject.meshRadioligand Assayen_US
dc.subject.meshReceptors, Muscarinic - Drug Effects - Physiologyen_US
dc.subject.meshScopolamine Hydrobromide - Metabolismen_US
dc.subject.meshSulfates - Metabolismen_US
dc.subject.meshSulfur Radioisotopesen_US
dc.subject.meshTrachea - Drug Effects - Innervation - Physiologyen_US
dc.subject.meshTritiumen_US
dc.titleOn muscarinic control of neurogenic mucus secretion in ferret tracheaen_US
dc.typeArticleen_US
dc.identifier.emailMak, JCW:judymak@hku.hken_US
dc.identifier.authorityMak, JCW=rp00352en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid8842014-
dc.identifier.scopuseid_2-s2.0-0029793984en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0029793984&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume494en_US
dc.identifier.issue2en_US
dc.identifier.spage577en_US
dc.identifier.epage586en_US
dc.identifier.isiWOS:A1996VA38000022-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridRamnarine, SI=16158344500en_US
dc.identifier.scopusauthoridHaddad, EB=7102803008en_US
dc.identifier.scopusauthoridKhawaja, AM=7003931509en_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US
dc.identifier.scopusauthoridRogers, DF=7402049007en_US

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