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The active fragments of ghrelin cross the blood–brain barrier and enter the brain to produce antinociceptive effects after systemic administration
G (1-5)-NH 2 , G (1-7)-NH 2 , and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood–brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. T...
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| Published in: | Canadian journal of physiology and pharmacology 2021-10, Vol.99 (10), p.1057-1068 |
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| container_end_page | 1068 |
| container_issue | 10 |
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| container_title | Canadian journal of physiology and pharmacology |
| container_volume | 99 |
| creator | Fan, Bao-wei Liu, Yong-ling Zhu, Gui-xian Wu, Bing Zhang, Min-min Deng, Qing Wang, Jing-lei Chen, Jia-xiang Han, Ren-wen Wei, Jie |
| description | G (1-5)-NH
2
, G (1-7)-NH
2
, and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood–brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. The antinociceptive effects of these fragments (2, 6, 20, and 60 nmol/mouse) were tested at 5, 10, 20, 30, 40, 50, and 60 min after intravenous (i.v.) injection. These fragments induced dose- and time-related antinociceptive effects relative to saline. Using the near infrared fluorescence imaging experiments, our results showed that these fragments could cross the brain–blood barrier and enter the brain. The antinociceptive effects of these fragments were completely antagonized by naloxone (intracerebroventricular, i.c.v.); however, naloxone methiodide (intraperitoneal, i.p.), which is the peripheral restricted opioid receptor antagonist, did not antagonize these antinociceptive effects. Furthermore, the GHS-R1α antagonist [D-Lys
3
]-GHRP-6 (i.c.v.) completely antagonized these antinociceptive effects, too. These results suggested that these fragments induced antinociceptive effects through central opioid receptors and GHS-R1α. In conclusion, our studies indicated that these active fragments of ghrelin could cross the brain–blood barrier and enter the brain and induce antinociceptive effects through central opioid receptors and GHS-R1α after intravenous injection. |
| doi_str_mv | 10.1139/cjpp-2020-0668 |
| format | article |
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2
, G (1-7)-NH
2
, and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood–brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. The antinociceptive effects of these fragments (2, 6, 20, and 60 nmol/mouse) were tested at 5, 10, 20, 30, 40, 50, and 60 min after intravenous (i.v.) injection. These fragments induced dose- and time-related antinociceptive effects relative to saline. Using the near infrared fluorescence imaging experiments, our results showed that these fragments could cross the brain–blood barrier and enter the brain. The antinociceptive effects of these fragments were completely antagonized by naloxone (intracerebroventricular, i.c.v.); however, naloxone methiodide (intraperitoneal, i.p.), which is the peripheral restricted opioid receptor antagonist, did not antagonize these antinociceptive effects. Furthermore, the GHS-R1α antagonist [D-Lys
3
]-GHRP-6 (i.c.v.) completely antagonized these antinociceptive effects, too. These results suggested that these fragments induced antinociceptive effects through central opioid receptors and GHS-R1α. In conclusion, our studies indicated that these active fragments of ghrelin could cross the brain–blood barrier and enter the brain and induce antinociceptive effects through central opioid receptors and GHS-R1α after intravenous injection.</description><identifier>ISSN: 0008-4212</identifier><identifier>EISSN: 1205-7541</identifier><identifier>DOI: 10.1139/cjpp-2020-0668</identifier><identifier>PMID: 34492212</identifier><language>eng</language><publisher>1840 Woodward Drive, Suite 1, Ottawa, ON K2C 0P7: NRC Research Press</publisher><subject>Acute Pain - drug therapy ; Acute Pain - etiology ; Acute Pain - metabolism ; Acute Pain - pathology ; Analgesics - pharmacology ; Animals ; Animals, Outbred Strains ; antinociception ; barrière hémo-encéphalique ; Blood-brain barrier ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - metabolism ; Brain - drug effects ; Brain - metabolism ; Ghrelin ; Ghrelin - administration & dosage ; Ghrelin - pharmacokinetics ; Ghrelin - pharmacology ; GHS-R1α ; Hot Temperature - adverse effects ; Injection ; Intravenous administration ; Male ; Mice ; Naloxone ; Narcotic Antagonists - pharmacology ; Narcotics ; Neuroimaging ; Opioid receptors ; Pain perception ; Physiological aspects ; Receptors, Ghrelin - antagonists & inhibitors ; Receptors, Ghrelin - metabolism ; Receptors, Opioid - chemistry ; Receptors, Opioid - metabolism ; récepteurs opioïdes</subject><ispartof>Canadian journal of physiology and pharmacology, 2021-10, Vol.99 (10), p.1057-1068</ispartof><rights>COPYRIGHT 2021 NRC Research Press</rights><rights>2021 Published by NRC Research Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c520t-dd239b742501d19239965bf51487ff46345c289f8734b623d672f09d270eee743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34492212$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fan, Bao-wei</creatorcontrib><creatorcontrib>Liu, Yong-ling</creatorcontrib><creatorcontrib>Zhu, Gui-xian</creatorcontrib><creatorcontrib>Wu, Bing</creatorcontrib><creatorcontrib>Zhang, Min-min</creatorcontrib><creatorcontrib>Deng, Qing</creatorcontrib><creatorcontrib>Wang, Jing-lei</creatorcontrib><creatorcontrib>Chen, Jia-xiang</creatorcontrib><creatorcontrib>Han, Ren-wen</creatorcontrib><creatorcontrib>Wei, Jie</creatorcontrib><title>The active fragments of ghrelin cross the blood–brain barrier and enter the brain to produce antinociceptive effects after systemic administration</title><title>Canadian journal of physiology and pharmacology</title><addtitle>Can J Physiol Pharmacol</addtitle><description>G (1-5)-NH
2
, G (1-7)-NH
2
, and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood–brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. The antinociceptive effects of these fragments (2, 6, 20, and 60 nmol/mouse) were tested at 5, 10, 20, 30, 40, 50, and 60 min after intravenous (i.v.) injection. These fragments induced dose- and time-related antinociceptive effects relative to saline. Using the near infrared fluorescence imaging experiments, our results showed that these fragments could cross the brain–blood barrier and enter the brain. The antinociceptive effects of these fragments were completely antagonized by naloxone (intracerebroventricular, i.c.v.); however, naloxone methiodide (intraperitoneal, i.p.), which is the peripheral restricted opioid receptor antagonist, did not antagonize these antinociceptive effects. Furthermore, the GHS-R1α antagonist [D-Lys
3
]-GHRP-6 (i.c.v.) completely antagonized these antinociceptive effects, too. These results suggested that these fragments induced antinociceptive effects through central opioid receptors and GHS-R1α. In conclusion, our studies indicated that these active fragments of ghrelin could cross the brain–blood barrier and enter the brain and induce antinociceptive effects through central opioid receptors and GHS-R1α after intravenous injection.</description><subject>Acute Pain - drug therapy</subject><subject>Acute Pain - etiology</subject><subject>Acute Pain - metabolism</subject><subject>Acute Pain - pathology</subject><subject>Analgesics - pharmacology</subject><subject>Animals</subject><subject>Animals, Outbred Strains</subject><subject>antinociception</subject><subject>barrière hémo-encéphalique</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Ghrelin</subject><subject>Ghrelin - administration & dosage</subject><subject>Ghrelin - pharmacokinetics</subject><subject>Ghrelin - pharmacology</subject><subject>GHS-R1α</subject><subject>Hot Temperature - adverse effects</subject><subject>Injection</subject><subject>Intravenous administration</subject><subject>Male</subject><subject>Mice</subject><subject>Naloxone</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Narcotics</subject><subject>Neuroimaging</subject><subject>Opioid receptors</subject><subject>Pain perception</subject><subject>Physiological aspects</subject><subject>Receptors, Ghrelin - antagonists & inhibitors</subject><subject>Receptors, Ghrelin - metabolism</subject><subject>Receptors, Opioid - chemistry</subject><subject>Receptors, Opioid - metabolism</subject><subject>récepteurs opioïdes</subject><issn>0008-4212</issn><issn>1205-7541</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqVkstu1DAUhiMEokNhyxJFsIFFii-5OMuq4lKpAgnK2nLs44xHiZ3aTkV3vAM8IU-CMx0ug0ZCyAv7HH_nP8fWn2WPMTrBmLYv5WaaCoIIKlBdszvZChNUFU1V4rvZCiHEipJgcpQ9CGGTwppRdj87omXZkpRfZd8u15ALGc015NqLfgQbQ-503q89DMbm0rsQ8piobnBOff_ytfMi5TvhvQGfC6vyVJNOW2Z7F10-eadmmaRtNNZJI2Ha9gCtQaYOQi8l4SZEGI3MhRqNNSF6EY2zD7N7WgwBHu324-zT61eXZ2-Li_dvzs9OLwpZERQLpQhtu6YkFcIKtylo66rTFS5Zo3VZ07KShLWaNbTsakJV3RCNWkUaBABNSY-z57e6adqrGULkowkShkFYcHPgpGoQbSrKWEKf_YVu3Oxtmm6hGsoqVKLfVC8G4MZql14kF1F-WjeMoQqxNlHFAaoHC14MzoI2Kb3HPz3Ay8lc8T-hkwNQWmr54IOqL_YKEhPhc-zFHAI___jhP9h3--xukK1zPGg-eTMKf8Mx4otn-eJZvniWL55NBU92Xzt3I6hf-E-TJgDfAtZLDwGEl-t_if4AzzP1lA</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Fan, Bao-wei</creator><creator>Liu, Yong-ling</creator><creator>Zhu, Gui-xian</creator><creator>Wu, Bing</creator><creator>Zhang, Min-min</creator><creator>Deng, Qing</creator><creator>Wang, Jing-lei</creator><creator>Chen, Jia-xiang</creator><creator>Han, Ren-wen</creator><creator>Wei, Jie</creator><general>NRC Research Press</general><general>Canadian Science Publishing NRC Research Press</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>ISN</scope><scope>ISR</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20211001</creationdate><title>The active fragments of ghrelin cross the blood–brain barrier and enter the brain to produce antinociceptive effects after systemic administration</title><author>Fan, Bao-wei ; Liu, Yong-ling ; Zhu, Gui-xian ; Wu, Bing ; Zhang, Min-min ; Deng, Qing ; Wang, Jing-lei ; Chen, Jia-xiang ; Han, Ren-wen ; Wei, Jie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-dd239b742501d19239965bf51487ff46345c289f8734b623d672f09d270eee743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acute Pain - drug therapy</topic><topic>Acute Pain - etiology</topic><topic>Acute Pain - metabolism</topic><topic>Acute Pain - pathology</topic><topic>Analgesics - pharmacology</topic><topic>Animals</topic><topic>Animals, Outbred Strains</topic><topic>antinociception</topic><topic>barrière hémo-encéphalique</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Ghrelin</topic><topic>Ghrelin - administration & dosage</topic><topic>Ghrelin - pharmacokinetics</topic><topic>Ghrelin - pharmacology</topic><topic>GHS-R1α</topic><topic>Hot Temperature - adverse effects</topic><topic>Injection</topic><topic>Intravenous administration</topic><topic>Male</topic><topic>Mice</topic><topic>Naloxone</topic><topic>Narcotic Antagonists - pharmacology</topic><topic>Narcotics</topic><topic>Neuroimaging</topic><topic>Opioid receptors</topic><topic>Pain perception</topic><topic>Physiological aspects</topic><topic>Receptors, Ghrelin - antagonists & inhibitors</topic><topic>Receptors, Ghrelin - metabolism</topic><topic>Receptors, Opioid - chemistry</topic><topic>Receptors, Opioid - metabolism</topic><topic>récepteurs opioïdes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fan, Bao-wei</creatorcontrib><creatorcontrib>Liu, Yong-ling</creatorcontrib><creatorcontrib>Zhu, Gui-xian</creatorcontrib><creatorcontrib>Wu, Bing</creatorcontrib><creatorcontrib>Zhang, Min-min</creatorcontrib><creatorcontrib>Deng, Qing</creatorcontrib><creatorcontrib>Wang, Jing-lei</creatorcontrib><creatorcontrib>Chen, Jia-xiang</creatorcontrib><creatorcontrib>Han, Ren-wen</creatorcontrib><creatorcontrib>Wei, Jie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Canadian journal of physiology and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fan, Bao-wei</au><au>Liu, Yong-ling</au><au>Zhu, Gui-xian</au><au>Wu, Bing</au><au>Zhang, Min-min</au><au>Deng, Qing</au><au>Wang, Jing-lei</au><au>Chen, Jia-xiang</au><au>Han, Ren-wen</au><au>Wei, Jie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The active fragments of ghrelin cross the blood–brain barrier and enter the brain to produce antinociceptive effects after systemic administration</atitle><jtitle>Canadian journal of physiology and pharmacology</jtitle><addtitle>Can J Physiol Pharmacol</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>99</volume><issue>10</issue><spage>1057</spage><epage>1068</epage><pages>1057-1068</pages><issn>0008-4212</issn><eissn>1205-7541</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>G (1-5)-NH
2
, G (1-7)-NH
2
, and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood–brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. The antinociceptive effects of these fragments (2, 6, 20, and 60 nmol/mouse) were tested at 5, 10, 20, 30, 40, 50, and 60 min after intravenous (i.v.) injection. These fragments induced dose- and time-related antinociceptive effects relative to saline. Using the near infrared fluorescence imaging experiments, our results showed that these fragments could cross the brain–blood barrier and enter the brain. The antinociceptive effects of these fragments were completely antagonized by naloxone (intracerebroventricular, i.c.v.); however, naloxone methiodide (intraperitoneal, i.p.), which is the peripheral restricted opioid receptor antagonist, did not antagonize these antinociceptive effects. Furthermore, the GHS-R1α antagonist [D-Lys
3
]-GHRP-6 (i.c.v.) completely antagonized these antinociceptive effects, too. These results suggested that these fragments induced antinociceptive effects through central opioid receptors and GHS-R1α. In conclusion, our studies indicated that these active fragments of ghrelin could cross the brain–blood barrier and enter the brain and induce antinociceptive effects through central opioid receptors and GHS-R1α after intravenous injection.</abstract><cop>1840 Woodward Drive, Suite 1, Ottawa, ON K2C 0P7</cop><pub>NRC Research Press</pub><pmid>34492212</pmid><doi>10.1139/cjpp-2020-0668</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-4212 |
| ispartof | Canadian journal of physiology and pharmacology, 2021-10, Vol.99 (10), p.1057-1068 |
| issn | 0008-4212 1205-7541 |
| language | eng |
| recordid | cdi_gale_infotraccpiq_678805089 |
| source | SPORTDiscus |
| subjects | Acute Pain - drug therapy Acute Pain - etiology Acute Pain - metabolism Acute Pain - pathology Analgesics - pharmacology Animals Animals, Outbred Strains antinociception barrière hémo-encéphalique Blood-brain barrier Blood-Brain Barrier - drug effects Blood-Brain Barrier - metabolism Brain - drug effects Brain - metabolism Ghrelin Ghrelin - administration & dosage Ghrelin - pharmacokinetics Ghrelin - pharmacology GHS-R1α Hot Temperature - adverse effects Injection Intravenous administration Male Mice Naloxone Narcotic Antagonists - pharmacology Narcotics Neuroimaging Opioid receptors Pain perception Physiological aspects Receptors, Ghrelin - antagonists & inhibitors Receptors, Ghrelin - metabolism Receptors, Opioid - chemistry Receptors, Opioid - metabolism récepteurs opioïdes |
| title | The active fragments of ghrelin cross the blood–brain barrier and enter the brain to produce antinociceptive effects after systemic administration |
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