Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit
Background & Aims: This study was designed to characterize [D-F5Phe6D-Ala11]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5–500 μg · kg−1...
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| Veröffentlicht in: | Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 2001-02, Vol.120 (2), p.361-368 |
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| container_title | Gastroenterology (New York, N.Y. 1943) |
| container_volume | 120 |
| creator | Degen, Lukas P. Peng, Fuping Collet, Annette Rossi, Livid Ketterer, Silvia Serrano, Yolanda Larsen, Finn Beglinger, Christoph Hildebrand, Pius |
| description | Background & Aims: This study was designed to characterize [D-F5Phe6D-Ala11]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5–500 μg · kg−1 · h−1) inhibits GRP-induced gallbladder contraction and plasma cholecystokinin (CCK) release in a dose-dependent fashion. Methods: Gastric emptying and small bowel transit of a solid meal were quantified using scintigraphy. Meal-stimulated gallbladder contraction was measured by sonography in a 2-period crossover design. Results: Intravenous BIM26226 potently inhibited gastric lag time (114 ± 7 vs. 41 ± 6 minutes [control]) and gastric emptying rate (0.11 ± 0.02%/min vs. 0.26 ± 0.04%/min [control]), whereas concomitant infusion of BIM26226 accelerated small bowel transit time (153 ± 41 vs. 262 ± 20 minutes [control]). A continuous liquid meal perfusion into the duodenum induced complete gallbladder contraction (t50%, 35 ± 4 minutes), which BIM26226 inhibited significantly (t50%, 64 ± 8 minutes). BIM26226 did not alter plasma CCK response, indicating that circulating CCK did not mediate these effects. Conclusions: These data show that BIM26226 is a potent antagonist of exogenous and endogenous GRP and suggest that GRP is a major physiologic regulator of gastric emptying, small bowel transit, and gallbladder contraction.
GASTROENTEROLOGY 2001;120:361-368 |
| doi_str_mv | 10.1053/gast.2001.21174 |
| format | Article |
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GASTROENTEROLOGY 2001;120:361-368</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1053/gast.2001.21174</identifier><identifier>PMID: 11159876</identifier><identifier>CODEN: GASTAB</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Biological and medical sciences ; Bombesin - administration & dosage ; Bombesin - adverse effects ; Bombesin - analogs & derivatives ; Cholecystokinin - blood ; Cross-Over Studies ; Duodenum - diagnostic imaging ; Duodenum - drug effects ; Duodenum - physiology ; Eating - physiology ; Fundamental and applied biological sciences. Psychology ; Gallbladder Emptying - drug effects ; Gallbladder Emptying - physiology ; Gastric Emptying - drug effects ; Gastric Emptying - physiology ; Gastrointestinal Motility - drug effects ; Gastrointestinal Motility - physiology ; Humans ; Male ; Middle Aged ; Peptide Fragments - administration & dosage ; Peptide Fragments - adverse effects ; Radionuclide Imaging ; Receptors, Bombesin - antagonists & inhibitors ; Single-Blind Method ; Stomach ; Vertebrates: digestive system</subject><ispartof>Gastroenterology (New York, N.Y. 1943), 2001-02, Vol.120 (2), p.361-368</ispartof><rights>2001 American Gastroenterological Association</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-8cda25881261ed7130f6f7cfdd83e555a8e05f154fcc3c924286a8373491a5de3</citedby><cites>FETCH-LOGICAL-c437t-8cda25881261ed7130f6f7cfdd83e555a8e05f154fcc3c924286a8373491a5de3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1053/gast.2001.21174$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=913242$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11159876$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Degen, Lukas P.</creatorcontrib><creatorcontrib>Peng, Fuping</creatorcontrib><creatorcontrib>Collet, Annette</creatorcontrib><creatorcontrib>Rossi, Livid</creatorcontrib><creatorcontrib>Ketterer, Silvia</creatorcontrib><creatorcontrib>Serrano, Yolanda</creatorcontrib><creatorcontrib>Larsen, Finn</creatorcontrib><creatorcontrib>Beglinger, Christoph</creatorcontrib><creatorcontrib>Hildebrand, Pius</creatorcontrib><title>Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit</title><title>Gastroenterology (New York, N.Y. 1943)</title><addtitle>Gastroenterology</addtitle><description>Background & Aims: This study was designed to characterize [D-F5Phe6D-Ala11]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5–500 μg · kg−1 · h−1) inhibits GRP-induced gallbladder contraction and plasma cholecystokinin (CCK) release in a dose-dependent fashion. Methods: Gastric emptying and small bowel transit of a solid meal were quantified using scintigraphy. Meal-stimulated gallbladder contraction was measured by sonography in a 2-period crossover design. Results: Intravenous BIM26226 potently inhibited gastric lag time (114 ± 7 vs. 41 ± 6 minutes [control]) and gastric emptying rate (0.11 ± 0.02%/min vs. 0.26 ± 0.04%/min [control]), whereas concomitant infusion of BIM26226 accelerated small bowel transit time (153 ± 41 vs. 262 ± 20 minutes [control]). A continuous liquid meal perfusion into the duodenum induced complete gallbladder contraction (t50%, 35 ± 4 minutes), which BIM26226 inhibited significantly (t50%, 64 ± 8 minutes). BIM26226 did not alter plasma CCK response, indicating that circulating CCK did not mediate these effects. Conclusions: These data show that BIM26226 is a potent antagonist of exogenous and endogenous GRP and suggest that GRP is a major physiologic regulator of gastric emptying, small bowel transit, and gallbladder contraction.
GASTROENTEROLOGY 2001;120:361-368</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Bombesin - administration & dosage</subject><subject>Bombesin - adverse effects</subject><subject>Bombesin - analogs & derivatives</subject><subject>Cholecystokinin - blood</subject><subject>Cross-Over Studies</subject><subject>Duodenum - diagnostic imaging</subject><subject>Duodenum - drug effects</subject><subject>Duodenum - physiology</subject><subject>Eating - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gallbladder Emptying - drug effects</subject><subject>Gallbladder Emptying - physiology</subject><subject>Gastric Emptying - drug effects</subject><subject>Gastric Emptying - physiology</subject><subject>Gastrointestinal Motility - drug effects</subject><subject>Gastrointestinal Motility - physiology</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Peptide Fragments - administration & dosage</subject><subject>Peptide Fragments - adverse effects</subject><subject>Radionuclide Imaging</subject><subject>Receptors, Bombesin - antagonists & inhibitors</subject><subject>Single-Blind Method</subject><subject>Stomach</subject><subject>Vertebrates: digestive system</subject><issn>0016-5085</issn><issn>1528-0012</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFvFCEUh4nR2LV69mZITLzNlgfDDHPUprYmTTRNPRMWHhWdgRXYxv73su6mnnp65OXj8XsfhLwFtgYmxdmdKXXNGYM1Bxj7Z2QFkquuNfhzsmpl6CRT8oS8KuUnY2wSCl6SEwCQkxqHFfnzaU72l3FIk6eXN99oRovbmnKhIf4Im1AL3T-Sg6W4bOtDiHfURNea87yZjXOYqU2xZmNrSJFudpUaa3HGbCoWWpYGtlntXEM0M21kLKG-Ji-8mQu-OdZT8v3zxe35VXf99fLL-cfrzvZirJ2yznCpFPAB0I0gmB_8aL1zSqCU0ihk0oPsvbXCTrznajBKjKKfwEiH4pR8OMzd5vR710LoJZQWbzYR067okQ2CcRANPDuANqdSMnq9zWEx-UED03vZeu9B72Xrf7LbjXfH0bvNgu4_f7TbgPdHwBRrZt82t6E8chOIlrdR04HCpuE-YNbFBowWXWifUbVL4ckIfwEJUJz5</recordid><startdate>20010201</startdate><enddate>20010201</enddate><creator>Degen, Lukas P.</creator><creator>Peng, Fuping</creator><creator>Collet, Annette</creator><creator>Rossi, Livid</creator><creator>Ketterer, Silvia</creator><creator>Serrano, Yolanda</creator><creator>Larsen, Finn</creator><creator>Beglinger, Christoph</creator><creator>Hildebrand, Pius</creator><general>Elsevier Inc</general><general>Elsevier</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>7X8</scope></search><sort><creationdate>20010201</creationdate><title>Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit</title><author>Degen, Lukas P. ; Peng, Fuping ; Collet, Annette ; Rossi, Livid ; Ketterer, Silvia ; Serrano, Yolanda ; Larsen, Finn ; Beglinger, Christoph ; Hildebrand, Pius</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-8cda25881261ed7130f6f7cfdd83e555a8e05f154fcc3c924286a8373491a5de3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Bombesin - administration & dosage</topic><topic>Bombesin - adverse effects</topic><topic>Bombesin - analogs & derivatives</topic><topic>Cholecystokinin - blood</topic><topic>Cross-Over Studies</topic><topic>Duodenum - diagnostic imaging</topic><topic>Duodenum - drug effects</topic><topic>Duodenum - physiology</topic><topic>Eating - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gallbladder Emptying - drug effects</topic><topic>Gallbladder Emptying - physiology</topic><topic>Gastric Emptying - drug effects</topic><topic>Gastric Emptying - physiology</topic><topic>Gastrointestinal Motility - drug effects</topic><topic>Gastrointestinal Motility - physiology</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Peptide Fragments - administration & dosage</topic><topic>Peptide Fragments - adverse effects</topic><topic>Radionuclide Imaging</topic><topic>Receptors, Bombesin - antagonists & inhibitors</topic><topic>Single-Blind Method</topic><topic>Stomach</topic><topic>Vertebrates: digestive system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Degen, Lukas P.</creatorcontrib><creatorcontrib>Peng, Fuping</creatorcontrib><creatorcontrib>Collet, Annette</creatorcontrib><creatorcontrib>Rossi, Livid</creatorcontrib><creatorcontrib>Ketterer, Silvia</creatorcontrib><creatorcontrib>Serrano, Yolanda</creatorcontrib><creatorcontrib>Larsen, Finn</creatorcontrib><creatorcontrib>Beglinger, Christoph</creatorcontrib><creatorcontrib>Hildebrand, Pius</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>MEDLINE - Academic</collection><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Degen, Lukas P.</au><au>Peng, Fuping</au><au>Collet, Annette</au><au>Rossi, Livid</au><au>Ketterer, Silvia</au><au>Serrano, Yolanda</au><au>Larsen, Finn</au><au>Beglinger, Christoph</au><au>Hildebrand, Pius</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit</atitle><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle><addtitle>Gastroenterology</addtitle><date>2001-02-01</date><risdate>2001</risdate><volume>120</volume><issue>2</issue><spage>361</spage><epage>368</epage><pages>361-368</pages><issn>0016-5085</issn><eissn>1528-0012</eissn><coden>GASTAB</coden><abstract>Background & Aims: This study was designed to characterize [D-F5Phe6D-Ala11]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5–500 μg · kg−1 · h−1) inhibits GRP-induced gallbladder contraction and plasma cholecystokinin (CCK) release in a dose-dependent fashion. Methods: Gastric emptying and small bowel transit of a solid meal were quantified using scintigraphy. Meal-stimulated gallbladder contraction was measured by sonography in a 2-period crossover design. Results: Intravenous BIM26226 potently inhibited gastric lag time (114 ± 7 vs. 41 ± 6 minutes [control]) and gastric emptying rate (0.11 ± 0.02%/min vs. 0.26 ± 0.04%/min [control]), whereas concomitant infusion of BIM26226 accelerated small bowel transit time (153 ± 41 vs. 262 ± 20 minutes [control]). A continuous liquid meal perfusion into the duodenum induced complete gallbladder contraction (t50%, 35 ± 4 minutes), which BIM26226 inhibited significantly (t50%, 64 ± 8 minutes). BIM26226 did not alter plasma CCK response, indicating that circulating CCK did not mediate these effects. Conclusions: These data show that BIM26226 is a potent antagonist of exogenous and endogenous GRP and suggest that GRP is a major physiologic regulator of gastric emptying, small bowel transit, and gallbladder contraction.
GASTROENTEROLOGY 2001;120:361-368</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>11159876</pmid><doi>10.1053/gast.2001.21174</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Biological and medical sciences Bombesin - administration & dosage Bombesin - adverse effects Bombesin - analogs & derivatives Cholecystokinin - blood Cross-Over Studies Duodenum - diagnostic imaging Duodenum - drug effects Duodenum - physiology Eating - physiology Fundamental and applied biological sciences. Psychology Gallbladder Emptying - drug effects Gallbladder Emptying - physiology Gastric Emptying - drug effects Gastric Emptying - physiology Gastrointestinal Motility - drug effects Gastrointestinal Motility - physiology Humans Male Middle Aged Peptide Fragments - administration & dosage Peptide Fragments - adverse effects Radionuclide Imaging Receptors, Bombesin - antagonists & inhibitors Single-Blind Method Stomach Vertebrates: digestive system |
| title | Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit |
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