Comparison of the effects of epithelium removal and of an enkephalinase inhibitor on the neurokinin‐induced contractions of guinea‐pig isolated trachea
1 The influence of epithelium removal and/or thiorphan on the effects of neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB)) and related peptides on airway contractility was investigated on the guinea‐pig isolated trachea. 2 Removing the tracheal epithelium significantly enhanced...
Gespeichert in:
| Veröffentlicht in: | British journal of pharmacology 1988-07, Vol.94 (3), p.675-684 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 684 |
|---|---|
| container_issue | 3 |
| container_start_page | 675 |
| container_title | British journal of pharmacology |
| container_volume | 94 |
| creator | Devillier, Philippe Advenier, Charles Drapeau, Guy Marsac, Jean Regoli, Domenico |
| description | 1
The influence of epithelium removal and/or thiorphan on the effects of neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB)) and related peptides on airway contractility was investigated on the guinea‐pig isolated trachea.
2
Removing the tracheal epithelium significantly enhanced the sensitivity but not the maximum contractile responses to the peptides.
3
After removal of the epithelial layer, the shifts to the left of the log concentration response curves were greater for SP and SP‐OMe (1.62 and 1.94 log units, respectively) than for two SP analogues substituted in position 9 namely [Pro9]SP sulfone and [β‐Ala,4 Sar9]SP(4–11)sulfone (0.66 and 0.68 log units, respectively). The leftward shifts for compounds related to NKA or NKB lay between 0.58 and 0.73 log units.
4
The leftward shifts of the log concentration‐response curves for SP, SP‐OMe, [Pro9]SP sulfone, [β‐Ala4, Sar9]SP(4–11) sulfone and NKA were of similar magnitude after removal of the epithelium or after pretreatment with thiorphan (10−5 m), an enkephalinase inhibitor, in the presence of epithelium. No significant additional shift of the curves to the left was observed with thiorphan plus epithelium removal.
5
The results obtained with the selective agonists for each of the three classes of neurokinin receptor (i.e NK1, NK2, NK3) suggest that the guinea‐pig trachea contains receptors for SP and NKA but few if any for NKB.
6
It was concluded that neurokinins and related peptides (especially SP and analogues not substituted in position 9) are degraded by enkephalinase mainly located in the tracheal epithelium and that the addition of thiorphan or epithelium removal results in an inhibition or loss of enkephalinase activity, thereby increasing similarly the potencies of these peptides. It was, therefore, suggested that the supersensitivity to neurokinins produced by epithelium removal was due neither to the elimination of a permeability barrier nor to reduced production of a relaxant factor, but mainly to reduced peptide degradation. |
| doi_str_mv | 10.1111/j.1476-5381.1988.tb11575.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1854024</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>78482988</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6045-f9418bfd9144265c8e60594b80412e68c3afe2023ce963f4ce7ef7fcce45bcc83</originalsourceid><addsrcrecordid>eNqVUstu1DAUjRCoDIVPQIoQYpdgJ3bisEDACChSJVjA2nKc64mnjh3spLS7fkL3_B1fgtOJRrBCeOPHOff4XJ2bJM8wynFcL_c5JnWV0ZLhHDeM5VOLMa1pfnUv2Ryh-8kGIVRnGDP2MHkUwh6hCNb0JDkpSIVwXW-Sn1s3jMLr4GzqVDr1kIJSIKewXGHU8cXoeUg9DO5SmFTYbkGETcFewNgLo60IkGrb61ZPzqdRaZGxMHt3oa22v25ute1mCV0qnZ28kJN29u6D3awtiEgY9S6NJoyYImuh9CAeJw-UMAGerPtp8u3D-6_bs-z888dP27fnmawQoZlqCGat6hpMSFFRyaBCtCEtQwQXUDFZCgUFKkoJTVUqIqEGVSspgdBWSlaeJq8PuuPcDtBJWDwaPno9CH_NndD8b8Tqnu_cJceMElSQKPBiFfDu-wxh4oMOEowRFtwceM0IK2JO_yRiilHTsDISXx2I0rsQPKijG4z4MgN8z5eg-RI0X2aArzPAr2Lx0z_7OZauoUf8-YqLIIVRXlipw5FWo6KhdOnqzYH2Qxu4_g8D_N2Xs7tj-Rvn4dYc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>15109983</pqid></control><display><type>article</type><title>Comparison of the effects of epithelium removal and of an enkephalinase inhibitor on the neurokinin‐induced contractions of guinea‐pig isolated trachea</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Devillier, Philippe ; Advenier, Charles ; Drapeau, Guy ; Marsac, Jean ; Regoli, Domenico</creator><creatorcontrib>Devillier, Philippe ; Advenier, Charles ; Drapeau, Guy ; Marsac, Jean ; Regoli, Domenico</creatorcontrib><description>1
The influence of epithelium removal and/or thiorphan on the effects of neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB)) and related peptides on airway contractility was investigated on the guinea‐pig isolated trachea.
2
Removing the tracheal epithelium significantly enhanced the sensitivity but not the maximum contractile responses to the peptides.
3
After removal of the epithelial layer, the shifts to the left of the log concentration response curves were greater for SP and SP‐OMe (1.62 and 1.94 log units, respectively) than for two SP analogues substituted in position 9 namely [Pro9]SP sulfone and [β‐Ala,4 Sar9]SP(4–11)sulfone (0.66 and 0.68 log units, respectively). The leftward shifts for compounds related to NKA or NKB lay between 0.58 and 0.73 log units.
4
The leftward shifts of the log concentration‐response curves for SP, SP‐OMe, [Pro9]SP sulfone, [β‐Ala4, Sar9]SP(4–11) sulfone and NKA were of similar magnitude after removal of the epithelium or after pretreatment with thiorphan (10−5 m), an enkephalinase inhibitor, in the presence of epithelium. No significant additional shift of the curves to the left was observed with thiorphan plus epithelium removal.
5
The results obtained with the selective agonists for each of the three classes of neurokinin receptor (i.e NK1, NK2, NK3) suggest that the guinea‐pig trachea contains receptors for SP and NKA but few if any for NKB.
6
It was concluded that neurokinins and related peptides (especially SP and analogues not substituted in position 9) are degraded by enkephalinase mainly located in the tracheal epithelium and that the addition of thiorphan or epithelium removal results in an inhibition or loss of enkephalinase activity, thereby increasing similarly the potencies of these peptides. It was, therefore, suggested that the supersensitivity to neurokinins produced by epithelium removal was due neither to the elimination of a permeability barrier nor to reduced production of a relaxant factor, but mainly to reduced peptide degradation.</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/j.1476-5381.1988.tb11575.x</identifier><identifier>PMID: 2460177</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Air breathing ; Airway Resistance - drug effects ; Animals ; Biological and medical sciences ; Epithelium - physiology ; Fundamental and applied biological sciences. Psychology ; Guinea Pigs ; In Vitro Techniques ; Male ; Neprilysin - antagonists & inhibitors ; Neurokinin A - pharmacology ; Neurokinin B - pharmacology ; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics ; Substance P - pharmacology ; Tachykinins - pharmacology ; Thiorphan - pharmacology ; Trachea - drug effects ; Vertebrates: respiratory system</subject><ispartof>British journal of pharmacology, 1988-07, Vol.94 (3), p.675-684</ispartof><rights>1988 British Pharmacological Society</rights><rights>1989 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6045-f9418bfd9144265c8e60594b80412e68c3afe2023ce963f4ce7ef7fcce45bcc83</citedby><cites>FETCH-LOGICAL-c6045-f9418bfd9144265c8e60594b80412e68c3afe2023ce963f4ce7ef7fcce45bcc83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1854024/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1854024/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7029554$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2460177$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Devillier, Philippe</creatorcontrib><creatorcontrib>Advenier, Charles</creatorcontrib><creatorcontrib>Drapeau, Guy</creatorcontrib><creatorcontrib>Marsac, Jean</creatorcontrib><creatorcontrib>Regoli, Domenico</creatorcontrib><title>Comparison of the effects of epithelium removal and of an enkephalinase inhibitor on the neurokinin‐induced contractions of guinea‐pig isolated trachea</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>1
The influence of epithelium removal and/or thiorphan on the effects of neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB)) and related peptides on airway contractility was investigated on the guinea‐pig isolated trachea.
2
Removing the tracheal epithelium significantly enhanced the sensitivity but not the maximum contractile responses to the peptides.
3
After removal of the epithelial layer, the shifts to the left of the log concentration response curves were greater for SP and SP‐OMe (1.62 and 1.94 log units, respectively) than for two SP analogues substituted in position 9 namely [Pro9]SP sulfone and [β‐Ala,4 Sar9]SP(4–11)sulfone (0.66 and 0.68 log units, respectively). The leftward shifts for compounds related to NKA or NKB lay between 0.58 and 0.73 log units.
4
The leftward shifts of the log concentration‐response curves for SP, SP‐OMe, [Pro9]SP sulfone, [β‐Ala4, Sar9]SP(4–11) sulfone and NKA were of similar magnitude after removal of the epithelium or after pretreatment with thiorphan (10−5 m), an enkephalinase inhibitor, in the presence of epithelium. No significant additional shift of the curves to the left was observed with thiorphan plus epithelium removal.
5
The results obtained with the selective agonists for each of the three classes of neurokinin receptor (i.e NK1, NK2, NK3) suggest that the guinea‐pig trachea contains receptors for SP and NKA but few if any for NKB.
6
It was concluded that neurokinins and related peptides (especially SP and analogues not substituted in position 9) are degraded by enkephalinase mainly located in the tracheal epithelium and that the addition of thiorphan or epithelium removal results in an inhibition or loss of enkephalinase activity, thereby increasing similarly the potencies of these peptides. It was, therefore, suggested that the supersensitivity to neurokinins produced by epithelium removal was due neither to the elimination of a permeability barrier nor to reduced production of a relaxant factor, but mainly to reduced peptide degradation.</description><subject>Air breathing</subject><subject>Airway Resistance - drug effects</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Epithelium - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Guinea Pigs</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Neprilysin - antagonists & inhibitors</subject><subject>Neurokinin A - pharmacology</subject><subject>Neurokinin B - pharmacology</subject><subject>Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics</subject><subject>Substance P - pharmacology</subject><subject>Tachykinins - pharmacology</subject><subject>Thiorphan - pharmacology</subject><subject>Trachea - drug effects</subject><subject>Vertebrates: respiratory system</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVUstu1DAUjRCoDIVPQIoQYpdgJ3bisEDACChSJVjA2nKc64mnjh3spLS7fkL3_B1fgtOJRrBCeOPHOff4XJ2bJM8wynFcL_c5JnWV0ZLhHDeM5VOLMa1pfnUv2Ryh-8kGIVRnGDP2MHkUwh6hCNb0JDkpSIVwXW-Sn1s3jMLr4GzqVDr1kIJSIKewXGHU8cXoeUg9DO5SmFTYbkGETcFewNgLo60IkGrb61ZPzqdRaZGxMHt3oa22v25ute1mCV0qnZ28kJN29u6D3awtiEgY9S6NJoyYImuh9CAeJw-UMAGerPtp8u3D-6_bs-z888dP27fnmawQoZlqCGat6hpMSFFRyaBCtCEtQwQXUDFZCgUFKkoJTVUqIqEGVSspgdBWSlaeJq8PuuPcDtBJWDwaPno9CH_NndD8b8Tqnu_cJceMElSQKPBiFfDu-wxh4oMOEowRFtwceM0IK2JO_yRiilHTsDISXx2I0rsQPKijG4z4MgN8z5eg-RI0X2aArzPAr2Lx0z_7OZauoUf8-YqLIIVRXlipw5FWo6KhdOnqzYH2Qxu4_g8D_N2Xs7tj-Rvn4dYc</recordid><startdate>198807</startdate><enddate>198807</enddate><creator>Devillier, Philippe</creator><creator>Advenier, Charles</creator><creator>Drapeau, Guy</creator><creator>Marsac, Jean</creator><creator>Regoli, Domenico</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>198807</creationdate><title>Comparison of the effects of epithelium removal and of an enkephalinase inhibitor on the neurokinin‐induced contractions of guinea‐pig isolated trachea</title><author>Devillier, Philippe ; Advenier, Charles ; Drapeau, Guy ; Marsac, Jean ; Regoli, Domenico</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6045-f9418bfd9144265c8e60594b80412e68c3afe2023ce963f4ce7ef7fcce45bcc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>Air breathing</topic><topic>Airway Resistance - drug effects</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Epithelium - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Guinea Pigs</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Neprilysin - antagonists & inhibitors</topic><topic>Neurokinin A - pharmacology</topic><topic>Neurokinin B - pharmacology</topic><topic>Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics</topic><topic>Substance P - pharmacology</topic><topic>Tachykinins - pharmacology</topic><topic>Thiorphan - pharmacology</topic><topic>Trachea - drug effects</topic><topic>Vertebrates: respiratory system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Devillier, Philippe</creatorcontrib><creatorcontrib>Advenier, Charles</creatorcontrib><creatorcontrib>Drapeau, Guy</creatorcontrib><creatorcontrib>Marsac, Jean</creatorcontrib><creatorcontrib>Regoli, Domenico</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Devillier, Philippe</au><au>Advenier, Charles</au><au>Drapeau, Guy</au><au>Marsac, Jean</au><au>Regoli, Domenico</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of the effects of epithelium removal and of an enkephalinase inhibitor on the neurokinin‐induced contractions of guinea‐pig isolated trachea</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>1988-07</date><risdate>1988</risdate><volume>94</volume><issue>3</issue><spage>675</spage><epage>684</epage><pages>675-684</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>1
The influence of epithelium removal and/or thiorphan on the effects of neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB)) and related peptides on airway contractility was investigated on the guinea‐pig isolated trachea.
2
Removing the tracheal epithelium significantly enhanced the sensitivity but not the maximum contractile responses to the peptides.
3
After removal of the epithelial layer, the shifts to the left of the log concentration response curves were greater for SP and SP‐OMe (1.62 and 1.94 log units, respectively) than for two SP analogues substituted in position 9 namely [Pro9]SP sulfone and [β‐Ala,4 Sar9]SP(4–11)sulfone (0.66 and 0.68 log units, respectively). The leftward shifts for compounds related to NKA or NKB lay between 0.58 and 0.73 log units.
4
The leftward shifts of the log concentration‐response curves for SP, SP‐OMe, [Pro9]SP sulfone, [β‐Ala4, Sar9]SP(4–11) sulfone and NKA were of similar magnitude after removal of the epithelium or after pretreatment with thiorphan (10−5 m), an enkephalinase inhibitor, in the presence of epithelium. No significant additional shift of the curves to the left was observed with thiorphan plus epithelium removal.
5
The results obtained with the selective agonists for each of the three classes of neurokinin receptor (i.e NK1, NK2, NK3) suggest that the guinea‐pig trachea contains receptors for SP and NKA but few if any for NKB.
6
It was concluded that neurokinins and related peptides (especially SP and analogues not substituted in position 9) are degraded by enkephalinase mainly located in the tracheal epithelium and that the addition of thiorphan or epithelium removal results in an inhibition or loss of enkephalinase activity, thereby increasing similarly the potencies of these peptides. It was, therefore, suggested that the supersensitivity to neurokinins produced by epithelium removal was due neither to the elimination of a permeability barrier nor to reduced production of a relaxant factor, but mainly to reduced peptide degradation.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>2460177</pmid><doi>10.1111/j.1476-5381.1988.tb11575.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-1188 |
| ispartof | British journal of pharmacology, 1988-07, Vol.94 (3), p.675-684 |
| issn | 0007-1188 1476-5381 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1854024 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Air breathing Airway Resistance - drug effects Animals Biological and medical sciences Epithelium - physiology Fundamental and applied biological sciences. Psychology Guinea Pigs In Vitro Techniques Male Neprilysin - antagonists & inhibitors Neurokinin A - pharmacology Neurokinin B - pharmacology Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics Substance P - pharmacology Tachykinins - pharmacology Thiorphan - pharmacology Trachea - drug effects Vertebrates: respiratory system |
| title | Comparison of the effects of epithelium removal and of an enkephalinase inhibitor on the neurokinin‐induced contractions of guinea‐pig isolated trachea |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T06%3A20%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comparison%20of%20the%20effects%20of%20epithelium%20removal%20and%20of%20an%20enkephalinase%20inhibitor%20on%20the%20neurokinin%E2%80%90induced%20contractions%20of%20guinea%E2%80%90pig%20isolated%20trachea&rft.jtitle=British%20journal%20of%20pharmacology&rft.au=Devillier,%20Philippe&rft.date=1988-07&rft.volume=94&rft.issue=3&rft.spage=675&rft.epage=684&rft.pages=675-684&rft.issn=0007-1188&rft.eissn=1476-5381&rft.coden=BJPCBM&rft_id=info:doi/10.1111/j.1476-5381.1988.tb11575.x&rft_dat=%3Cproquest_pubme%3E78482988%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=15109983&rft_id=info:pmid/2460177&rfr_iscdi=true |