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Article: Cholinergic control of human airways in vitro following extrinsic denervation of the human respiratory tract by heart-lung transplantation

TitleCholinergic control of human airways in vitro following extrinsic denervation of the human respiratory tract by heart-lung transplantation
Authors
Issue Date1990
PublisherAmerican Thoracic Society. The Journal's web site is located at http://ajrccm.atsjournals.org
Citation
American Review Of Respiratory Disease, 1990, v. 142 n. 5, p. 1030-1033 How to Cite?
AbstractIn heart-lung transplantation (HLT), the airways have been assumed to be denervated since cholinergic, adrenergic, and sensory nerves are severed. Challenge studies of such patients suggest that there is an increase in airway responsiveness to inhaled cholinergic agonists, which may be explained by denervation hypersensitivity of muscarinic receptors on airway smooth muscle. We have studied the cholinergic control of airways from lungs removed from five patients (8 to 31 yr of age) undergoing retransplantation because of rejection-related bronchiolitis, with time since transplantation ranging from 12 to 32 months. These airways were compared with airways obtained from eight heart donors (24 to 42 yr of age) and from five patients undergoing surgical lobectomy for bronchial carcinoma (54 to 72 yr of age). Bronchial rings (distal lobar and subsegmental) were mounted in organ baths and isometric contractile responses measured. Contractile responses to acetylcholine (ACh, 10 nM to 10 mM) and to electrical field stimulation (EFS) (40 V, 0.5 ms, 1 to 64 Hz for 15 s) were determined. Transplant and control airways showed the same response to ACh, with mean EC50 values of 61.0 ± 0.32 μM for HLT patients, 57.6 ± 0.24 μM for donor patients, and 48.7 ± 1.2 μM for lobectomy patients, suggesting no denervation hypersensitivity of muscarinic receptors. EFS, which activates postganglionic cholinergic nerves, caused similar frequency responses in both transplant and control airways, suggesting that postganglionic nerves are intact. [3H]quinuclidinyl benzilate binding to membranes prepared from lung was performed to determine muscarinic binding characteristics. There was a small but insignificant increase in receptor density (B(max) = 61.4 ± 7.5 in HLT and 46.1 ± 7.1 fmol/mg protein in control patients) and no difference in the binding affinity (K(d) = 0.48 ± 0.08 in HLT and 0.37 ± 0.06 nM in control patients), indicating no alteration in muscarinic receptors with denervation. We conclude that surgically denervated human airways from lung transplant patients have normally functioning postganglionic nerves and no change in cholinergic responsiveness or receptors, presumably because parasympathetic neurons survive. Denervation hypersensitivity cannot account for the increased cholinergic responsiveness observed in these patients.
Persistent Identifierhttp://hdl.handle.net/10722/161829
ISSN
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorStretton, CDen_US
dc.contributor.authorMak, JCWen_US
dc.contributor.authorBelvisi, MGen_US
dc.contributor.authorYacoub, MHen_US
dc.contributor.authorBarnes, PJen_US
dc.date.accessioned2012-09-05T05:15:21Z-
dc.date.available2012-09-05T05:15:21Z-
dc.date.issued1990en_US
dc.identifier.citationAmerican Review Of Respiratory Disease, 1990, v. 142 n. 5, p. 1030-1033en_US
dc.identifier.issn0003-0805en_US
dc.identifier.urihttp://hdl.handle.net/10722/161829-
dc.description.abstractIn heart-lung transplantation (HLT), the airways have been assumed to be denervated since cholinergic, adrenergic, and sensory nerves are severed. Challenge studies of such patients suggest that there is an increase in airway responsiveness to inhaled cholinergic agonists, which may be explained by denervation hypersensitivity of muscarinic receptors on airway smooth muscle. We have studied the cholinergic control of airways from lungs removed from five patients (8 to 31 yr of age) undergoing retransplantation because of rejection-related bronchiolitis, with time since transplantation ranging from 12 to 32 months. These airways were compared with airways obtained from eight heart donors (24 to 42 yr of age) and from five patients undergoing surgical lobectomy for bronchial carcinoma (54 to 72 yr of age). Bronchial rings (distal lobar and subsegmental) were mounted in organ baths and isometric contractile responses measured. Contractile responses to acetylcholine (ACh, 10 nM to 10 mM) and to electrical field stimulation (EFS) (40 V, 0.5 ms, 1 to 64 Hz for 15 s) were determined. Transplant and control airways showed the same response to ACh, with mean EC50 values of 61.0 ± 0.32 μM for HLT patients, 57.6 ± 0.24 μM for donor patients, and 48.7 ± 1.2 μM for lobectomy patients, suggesting no denervation hypersensitivity of muscarinic receptors. EFS, which activates postganglionic cholinergic nerves, caused similar frequency responses in both transplant and control airways, suggesting that postganglionic nerves are intact. [3H]quinuclidinyl benzilate binding to membranes prepared from lung was performed to determine muscarinic binding characteristics. There was a small but insignificant increase in receptor density (B(max) = 61.4 ± 7.5 in HLT and 46.1 ± 7.1 fmol/mg protein in control patients) and no difference in the binding affinity (K(d) = 0.48 ± 0.08 in HLT and 0.37 ± 0.06 nM in control patients), indicating no alteration in muscarinic receptors with denervation. We conclude that surgically denervated human airways from lung transplant patients have normally functioning postganglionic nerves and no change in cholinergic responsiveness or receptors, presumably because parasympathetic neurons survive. Denervation hypersensitivity cannot account for the increased cholinergic responsiveness observed in these patients.en_US
dc.languageengen_US
dc.publisherAmerican Thoracic Society. The Journal's web site is located at http://ajrccm.atsjournals.orgen_US
dc.relation.ispartofAmerican Review of Respiratory Diseaseen_US
dc.subject.meshAcetylcholine - Pharmacologyen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdulten_US
dc.subject.meshBronchi - Drug Effects - Innervation - Physiopathologyen_US
dc.subject.meshBronchoconstriction - Drug Effectsen_US
dc.subject.meshChilden_US
dc.subject.meshDenervationen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshElectric Stimulationen_US
dc.subject.meshFemaleen_US
dc.subject.meshHeart Transplantationen_US
dc.subject.meshHumansen_US
dc.subject.meshIsoproterenol - Pharmacologyen_US
dc.subject.meshLung Transplantationen_US
dc.subject.meshMaleen_US
dc.subject.meshReceptors, Cholinergic - Metabolism - Physiologyen_US
dc.titleCholinergic control of human airways in vitro following extrinsic denervation of the human respiratory tract by heart-lung transplantationen_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.doi10.1164/ajrccm/142.5.1030-
dc.identifier.pmid2240824-
dc.identifier.scopuseid_2-s2.0-0025172956en_US
dc.identifier.volume142en_US
dc.identifier.issue5en_US
dc.identifier.spage1030en_US
dc.identifier.epage1033en_US
dc.identifier.isiWOS:A1990EG08800009-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridStretton, CD=6701549267en_US
dc.identifier.scopusauthoridMak, JCW=7103323094en_US
dc.identifier.scopusauthoridBelvisi, MG=35400532900en_US
dc.identifier.scopusauthoridYacoub, MH=36041927900en_US
dc.identifier.scopusauthoridBarnes, PJ=36064679400en_US

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