Contribution of opioid and neurotensin receptors in the anti‐inflammatory activity of PK20 hybrid compound in murine airways
PK20 is an anti‐inflammatory hybrid compound, composed of an endomorphin‐2‐like and neurotensin‐like fragments. The aim of the present study is to assess the contribution of particular pharmacophores to the activity of the hybrid tested. For this purpose, airway hyperresponsiveness, accumulation of...
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| Veröffentlicht in: | Clinical and experimental pharmacology & physiology 2021-08, Vol.48 (8), p.1162-1170 |
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| container_title | Clinical and experimental pharmacology & physiology |
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| creator | Russjan, Ewelina Zając, Dominika Sulejczak, Dorota Kleczkowska, Patrycja Kaczyńska, Katarzyna |
| description | PK20 is an anti‐inflammatory hybrid compound, composed of an endomorphin‐2‐like and neurotensin‐like fragments. The aim of the present study is to assess the contribution of particular pharmacophores to the activity of the hybrid tested. For this purpose, airway hyperresponsiveness, accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF), concentration of mouse mast cell protease, malondialdehyde and secretory phospholipase 2 activity in lung tissue, as well as production of pro‐inflammatory cytokines in BALF and lung were determined by using murine model of non‐atopic asthma. Blocking either neurotensin receptors or mu opioid receptors did not alter the potential of PK20 in reducing airway hyperresponsiveness. In studies of inflammatory cells, the beneficial effect of the entire peptide occurs to be mediated by the stimulation of neurotensin receptors. However, regarding cytokine and biochemical assays, pretreatment with both receptor antagonists resulted in a different effect on its activity depending on the parameter studied. To conclude, the activation of both the opioid and neurotensin receptors seems to be necessary to induce the full anti‐inflammatory activity of the hybrid compound. |
| doi_str_mv | 10.1111/1440-1681.13505 |
| format | Article |
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The aim of the present study is to assess the contribution of particular pharmacophores to the activity of the hybrid tested. For this purpose, airway hyperresponsiveness, accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF), concentration of mouse mast cell protease, malondialdehyde and secretory phospholipase 2 activity in lung tissue, as well as production of pro‐inflammatory cytokines in BALF and lung were determined by using murine model of non‐atopic asthma. Blocking either neurotensin receptors or mu opioid receptors did not alter the potential of PK20 in reducing airway hyperresponsiveness. In studies of inflammatory cells, the beneficial effect of the entire peptide occurs to be mediated by the stimulation of neurotensin receptors. However, regarding cytokine and biochemical assays, pretreatment with both receptor antagonists resulted in a different effect on its activity depending on the parameter studied. To conclude, the activation of both the opioid and neurotensin receptors seems to be necessary to induce the full anti‐inflammatory activity of the hybrid compound.</description><identifier>ISSN: 0305-1870</identifier><identifier>ISSN: 1440-1681</identifier><identifier>EISSN: 1440-1681</identifier><identifier>DOI: 10.1111/1440-1681.13505</identifier><identifier>PMID: 33851456</identifier><language>eng</language><publisher>Australia: Wiley Subscription Services, Inc</publisher><subject>airway hyperresponsiveness ; Animal models ; Animals ; Anti-Inflammatory Agents - pharmacology ; Asthma ; Atopy ; Bronchoalveolar Lavage Fluid - chemistry ; Bronchus ; Cytokines ; Cytokines - metabolism ; Endomorphins ; endomorphin‐2 ; Female ; hybrid peptide ; Inflammation ; Lung - drug effects ; Lung - metabolism ; Lungs ; Male ; Malondialdehyde ; Mice ; Mice, Inbred BALB C ; Narcotics ; Neurotensin ; Neurotensin - metabolism ; Neurotensin - pharmacology ; Neurotensin receptors ; Oligopeptides - pharmacology ; Opioid receptors (type mu) ; Pharmacophores ; Receptors ; Receptors, Neurotensin - antagonists & inhibitors ; Receptors, Neurotensin - metabolism ; Receptors, Opioid - metabolism ; Respiratory tract</subject><ispartof>Clinical and experimental pharmacology & physiology, 2021-08, Vol.48 (8), p.1162-1170</ispartof><rights>2021 John Wiley & Sons Australia, Ltd</rights><rights>2021 John Wiley & Sons Australia, Ltd.</rights><rights>Copyright © 2021 John Wiley & Sons Australia, Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3715-ce88dbafe9847c4bfb24e19b73c03d6da2ec69b96085b5be376b68283e41fc1b3</citedby><cites>FETCH-LOGICAL-c3715-ce88dbafe9847c4bfb24e19b73c03d6da2ec69b96085b5be376b68283e41fc1b3</cites><orcidid>0000-0002-9597-454X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2F1440-1681.13505$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2F1440-1681.13505$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33851456$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Russjan, Ewelina</creatorcontrib><creatorcontrib>Zając, Dominika</creatorcontrib><creatorcontrib>Sulejczak, Dorota</creatorcontrib><creatorcontrib>Kleczkowska, Patrycja</creatorcontrib><creatorcontrib>Kaczyńska, Katarzyna</creatorcontrib><title>Contribution of opioid and neurotensin receptors in the anti‐inflammatory activity of PK20 hybrid compound in murine airways</title><title>Clinical and experimental pharmacology & physiology</title><addtitle>Clin Exp Pharmacol Physiol</addtitle><description>PK20 is an anti‐inflammatory hybrid compound, composed of an endomorphin‐2‐like and neurotensin‐like fragments. The aim of the present study is to assess the contribution of particular pharmacophores to the activity of the hybrid tested. For this purpose, airway hyperresponsiveness, accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF), concentration of mouse mast cell protease, malondialdehyde and secretory phospholipase 2 activity in lung tissue, as well as production of pro‐inflammatory cytokines in BALF and lung were determined by using murine model of non‐atopic asthma. Blocking either neurotensin receptors or mu opioid receptors did not alter the potential of PK20 in reducing airway hyperresponsiveness. In studies of inflammatory cells, the beneficial effect of the entire peptide occurs to be mediated by the stimulation of neurotensin receptors. However, regarding cytokine and biochemical assays, pretreatment with both receptor antagonists resulted in a different effect on its activity depending on the parameter studied. To conclude, the activation of both the opioid and neurotensin receptors seems to be necessary to induce the full anti‐inflammatory activity of the hybrid compound.</description><subject>airway hyperresponsiveness</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Asthma</subject><subject>Atopy</subject><subject>Bronchoalveolar Lavage Fluid - chemistry</subject><subject>Bronchus</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Endomorphins</subject><subject>endomorphin‐2</subject><subject>Female</subject><subject>hybrid peptide</subject><subject>Inflammation</subject><subject>Lung - drug effects</subject><subject>Lung - metabolism</subject><subject>Lungs</subject><subject>Male</subject><subject>Malondialdehyde</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Narcotics</subject><subject>Neurotensin</subject><subject>Neurotensin - metabolism</subject><subject>Neurotensin - pharmacology</subject><subject>Neurotensin receptors</subject><subject>Oligopeptides - pharmacology</subject><subject>Opioid receptors (type mu)</subject><subject>Pharmacophores</subject><subject>Receptors</subject><subject>Receptors, Neurotensin - antagonists & inhibitors</subject><subject>Receptors, Neurotensin - metabolism</subject><subject>Receptors, Opioid - metabolism</subject><subject>Respiratory tract</subject><issn>0305-1870</issn><issn>1440-1681</issn><issn>1440-1681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkT1v1TAUhq0KRC-FuRuKxNIlrR1_xBmrq1IQlegAs2U7J6qrxA620ypLxU_ob-wvwZdbOrDg5cj28z460ovQMcGnpJwzwhiuiZDklFCO-QHavLy8QhtMMa-JbPEhepvSLcaYY0HfoENKJSeMiw162AafozNLdsFXYajC7ILrK-37ysMSQwafnK8iWJhziKkql3wDBcju6dej88Oop0mXr7XSNrs7l9ed5_prg6ub1cQis2Gaw1KMJTst0fkSd_Fer-kdej3oMcH753mEfny6-L79XF99u_yyPb-qLW0Jry1I2Rs9QCdZa5kZTMOAdKalFtNe9LoBKzrTCSy54QZoK4yQjaTAyGCJoUfoZO-dY_i5QMpqcsnCOGoPYUmq4aRpm040rKAf_0FvwxJ92a5QrCUUCyEKdbanbAwpRRjUHN2k46oIVrtq1K4ItStC_ammJD48exczQf_C_-2iAHwP3LsR1v_51Pbiei_-DYkvmuE</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Russjan, Ewelina</creator><creator>Zając, Dominika</creator><creator>Sulejczak, Dorota</creator><creator>Kleczkowska, Patrycja</creator><creator>Kaczyńska, Katarzyna</creator><general>Wiley Subscription Services, Inc</general><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>7QP</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9597-454X</orcidid></search><sort><creationdate>202108</creationdate><title>Contribution of opioid and neurotensin receptors in the anti‐inflammatory activity of PK20 hybrid compound in murine airways</title><author>Russjan, Ewelina ; Zając, Dominika ; Sulejczak, Dorota ; Kleczkowska, Patrycja ; Kaczyńska, Katarzyna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3715-ce88dbafe9847c4bfb24e19b73c03d6da2ec69b96085b5be376b68283e41fc1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>airway hyperresponsiveness</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Asthma</topic><topic>Atopy</topic><topic>Bronchoalveolar Lavage Fluid - chemistry</topic><topic>Bronchus</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Endomorphins</topic><topic>endomorphin‐2</topic><topic>Female</topic><topic>hybrid peptide</topic><topic>Inflammation</topic><topic>Lung - drug effects</topic><topic>Lung - metabolism</topic><topic>Lungs</topic><topic>Male</topic><topic>Malondialdehyde</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Narcotics</topic><topic>Neurotensin</topic><topic>Neurotensin - metabolism</topic><topic>Neurotensin - pharmacology</topic><topic>Neurotensin receptors</topic><topic>Oligopeptides - pharmacology</topic><topic>Opioid receptors (type mu)</topic><topic>Pharmacophores</topic><topic>Receptors</topic><topic>Receptors, Neurotensin - antagonists & inhibitors</topic><topic>Receptors, Neurotensin - metabolism</topic><topic>Receptors, Opioid - metabolism</topic><topic>Respiratory tract</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Russjan, Ewelina</creatorcontrib><creatorcontrib>Zając, Dominika</creatorcontrib><creatorcontrib>Sulejczak, Dorota</creatorcontrib><creatorcontrib>Kleczkowska, Patrycja</creatorcontrib><creatorcontrib>Kaczyńska, Katarzyna</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical and experimental pharmacology & physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Russjan, Ewelina</au><au>Zając, Dominika</au><au>Sulejczak, Dorota</au><au>Kleczkowska, Patrycja</au><au>Kaczyńska, Katarzyna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Contribution of opioid and neurotensin receptors in the anti‐inflammatory activity of PK20 hybrid compound in murine airways</atitle><jtitle>Clinical and experimental pharmacology & physiology</jtitle><addtitle>Clin Exp Pharmacol Physiol</addtitle><date>2021-08</date><risdate>2021</risdate><volume>48</volume><issue>8</issue><spage>1162</spage><epage>1170</epage><pages>1162-1170</pages><issn>0305-1870</issn><issn>1440-1681</issn><eissn>1440-1681</eissn><abstract>PK20 is an anti‐inflammatory hybrid compound, composed of an endomorphin‐2‐like and neurotensin‐like fragments. The aim of the present study is to assess the contribution of particular pharmacophores to the activity of the hybrid tested. For this purpose, airway hyperresponsiveness, accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF), concentration of mouse mast cell protease, malondialdehyde and secretory phospholipase 2 activity in lung tissue, as well as production of pro‐inflammatory cytokines in BALF and lung were determined by using murine model of non‐atopic asthma. Blocking either neurotensin receptors or mu opioid receptors did not alter the potential of PK20 in reducing airway hyperresponsiveness. In studies of inflammatory cells, the beneficial effect of the entire peptide occurs to be mediated by the stimulation of neurotensin receptors. However, regarding cytokine and biochemical assays, pretreatment with both receptor antagonists resulted in a different effect on its activity depending on the parameter studied. To conclude, the activation of both the opioid and neurotensin receptors seems to be necessary to induce the full anti‐inflammatory activity of the hybrid compound.</abstract><cop>Australia</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33851456</pmid><doi>10.1111/1440-1681.13505</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-9597-454X</orcidid></addata></record> |
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| subjects | airway hyperresponsiveness Animal models Animals Anti-Inflammatory Agents - pharmacology Asthma Atopy Bronchoalveolar Lavage Fluid - chemistry Bronchus Cytokines Cytokines - metabolism Endomorphins endomorphin‐2 Female hybrid peptide Inflammation Lung - drug effects Lung - metabolism Lungs Male Malondialdehyde Mice Mice, Inbred BALB C Narcotics Neurotensin Neurotensin - metabolism Neurotensin - pharmacology Neurotensin receptors Oligopeptides - pharmacology Opioid receptors (type mu) Pharmacophores Receptors Receptors, Neurotensin - antagonists & inhibitors Receptors, Neurotensin - metabolism Receptors, Opioid - metabolism Respiratory tract |
| title | Contribution of opioid and neurotensin receptors in the anti‐inflammatory activity of PK20 hybrid compound in murine airways |
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