Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans
Background/Aims: The role of cholecystokinin (CCK) in the regulation of gastric acid secretion is still controversial. This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a pl...
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| Veröffentlicht in: | Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 1994-12, Vol.107 (6), p.1610-1620 |
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| container_title | Gastroenterology (New York, N.Y. 1943) |
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| creator | Schmidt, Wolfgang E. Schenk, Stefan Nustede, Rainer Holst, Jens J. Fölsch, Ulrich R. Creutzfeldt, Werner |
| description | Background/Aims: The role of cholecystokinin (CCK) in the regulation of gastric acid secretion is still controversial. This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a placebo-controlled study. Methods: Acid output was studied in eight subjects who received intravenously gastrin-17 (15, 30, and 60 pmol·kg−1·h−1); gastrin-17 plus lox; cholecystokinin octapeptide (CCK-8) (15, 30, and 60 pmol·kg−1·h−1); CCK-8 plus lox; or gastrin plus CCK-8. Sham feeding-induced acid output and meal-stimulated gastrin secretion were studied during lox infusion. Results: Gastrin-17 dose-dependently stimulated acid output to near-maximal levels. CCK-8 (15 pmol· kg−1·h−1) increased acid secretion 2.5-fold over basal; higher infusion rates had less or no effect. When combined with lox, CCK-8 produced a near-maximal acid response (6-fold over basal). CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67%. Meal-stimulated plasma gastrin concentrations were elevated 3.2-fold, whereas sham feeding-induced acid secretion was not modified by lox. Conclusions: Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion. A CCK-mediated stimulation of paracrine somatostatin secretion from antrat and fundic D cells represents a candidate mechanism for the inhibition of the parietal and gastrin cell in humans. |
| doi_str_mv | 10.1016/0016-5085(94)90799-4 |
| format | Article |
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This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a placebo-controlled study. Methods: Acid output was studied in eight subjects who received intravenously gastrin-17 (15, 30, and 60 pmol·kg−1·h−1); gastrin-17 plus lox; cholecystokinin octapeptide (CCK-8) (15, 30, and 60 pmol·kg−1·h−1); CCK-8 plus lox; or gastrin plus CCK-8. Sham feeding-induced acid output and meal-stimulated gastrin secretion were studied during lox infusion. Results: Gastrin-17 dose-dependently stimulated acid output to near-maximal levels. CCK-8 (15 pmol· kg−1·h−1) increased acid secretion 2.5-fold over basal; higher infusion rates had less or no effect. When combined with lox, CCK-8 produced a near-maximal acid response (6-fold over basal). CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67%. Meal-stimulated plasma gastrin concentrations were elevated 3.2-fold, whereas sham feeding-induced acid secretion was not modified by lox. Conclusions: Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion. A CCK-mediated stimulation of paracrine somatostatin secretion from antrat and fundic D cells represents a candidate mechanism for the inhibition of the parietal and gastrin cell in humans.</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1016/0016-5085(94)90799-4</identifier><identifier>PMID: 7958670</identifier><identifier>CODEN: GASTAB</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Biological and medical sciences ; Cholecystokinin - pharmacology ; Cholecystokinin - physiology ; Eating ; Fundamental and applied biological sciences. Psychology ; Gastric Acid - metabolism ; Gastric Mucosa - drug effects ; Gastric Mucosa - metabolism ; Gastrins - metabolism ; Gastrins - pharmacology ; Gastrointestinal hormones ; Humans ; Male ; Proglumide - analogs & derivatives ; Proglumide - pharmacology ; Radioimmunoassay ; Receptors, Cholecystokinin - antagonists & inhibitors ; Somatostatin - blood ; Stomach - drug effects ; Vertebrates: digestive system</subject><ispartof>Gastroenterology (New York, N.Y. 1943), 1994-12, Vol.107 (6), p.1610-1620</ispartof><rights>1994</rights><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-94aefa510acfddc1e9e9bc66b924fc810dbfc264ca539d9c385be7c0f44662053</citedby><cites>FETCH-LOGICAL-c452t-94aefa510acfddc1e9e9bc66b924fc810dbfc264ca539d9c385be7c0f44662053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0016508594907994$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3355360$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7958670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmidt, Wolfgang E.</creatorcontrib><creatorcontrib>Schenk, Stefan</creatorcontrib><creatorcontrib>Nustede, Rainer</creatorcontrib><creatorcontrib>Holst, Jens J.</creatorcontrib><creatorcontrib>Fölsch, Ulrich R.</creatorcontrib><creatorcontrib>Creutzfeldt, Werner</creatorcontrib><title>Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans</title><title>Gastroenterology (New York, N.Y. 1943)</title><addtitle>Gastroenterology</addtitle><description>Background/Aims: The role of cholecystokinin (CCK) in the regulation of gastric acid secretion is still controversial. This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a placebo-controlled study. Methods: Acid output was studied in eight subjects who received intravenously gastrin-17 (15, 30, and 60 pmol·kg−1·h−1); gastrin-17 plus lox; cholecystokinin octapeptide (CCK-8) (15, 30, and 60 pmol·kg−1·h−1); CCK-8 plus lox; or gastrin plus CCK-8. Sham feeding-induced acid output and meal-stimulated gastrin secretion were studied during lox infusion. Results: Gastrin-17 dose-dependently stimulated acid output to near-maximal levels. CCK-8 (15 pmol· kg−1·h−1) increased acid secretion 2.5-fold over basal; higher infusion rates had less or no effect. When combined with lox, CCK-8 produced a near-maximal acid response (6-fold over basal). CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67%. Meal-stimulated plasma gastrin concentrations were elevated 3.2-fold, whereas sham feeding-induced acid secretion was not modified by lox. Conclusions: Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion. A CCK-mediated stimulation of paracrine somatostatin secretion from antrat and fundic D cells represents a candidate mechanism for the inhibition of the parietal and gastrin cell in humans.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Cholecystokinin - pharmacology</subject><subject>Cholecystokinin - physiology</subject><subject>Eating</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastric Acid - metabolism</subject><subject>Gastric Mucosa - drug effects</subject><subject>Gastric Mucosa - metabolism</subject><subject>Gastrins - metabolism</subject><subject>Gastrins - pharmacology</subject><subject>Gastrointestinal hormones</subject><subject>Humans</subject><subject>Male</subject><subject>Proglumide - analogs & derivatives</subject><subject>Proglumide - pharmacology</subject><subject>Radioimmunoassay</subject><subject>Receptors, Cholecystokinin - antagonists & inhibitors</subject><subject>Somatostatin - blood</subject><subject>Stomach - drug effects</subject><subject>Vertebrates: digestive system</subject><issn>0016-5085</issn><issn>1528-0012</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2PFCEURYnRjO3oP9CEhTG6KIUqoIqNien4lUziRteEejx60GpogZpk_r203Wl3boDknntDDiHPOXvLGVfvWDs6ySb5Wos3mo1ad-IB2XDZT13L-odkc0Eekyel_GSM6WHiV-Rq1HJSI9uQtL1NC8J9qelXiCHSUKilEXe2hjukGXfrYmvKNHm6s6XmANRCcLQgZKwhRWqjo4dU6iG3V7BLKy1oC_6rtNVIb9e9jeUpeeTtUvDZ-b4mPz59_L790t18-_x1--GmAyH72mlh0VvJmQXvHHDUqGdQata98DBx5mYPvRJg5aCdhmGSM47AvBBK9UwO1-TVafeQ0-8VSzX7UACXxUZMazGjaiNyVA0UJxByKiWjN4cc9jbfG87M0bM5SjRHiUYL89ezEa324ry_znt0l9JZbMtfnnNbwC6-uYFQLtgwSDmoI_b-hGFzcRcwmwIBI6ALGaEal8L___EHUqybwQ</recordid><startdate>19941201</startdate><enddate>19941201</enddate><creator>Schmidt, Wolfgang E.</creator><creator>Schenk, Stefan</creator><creator>Nustede, Rainer</creator><creator>Holst, Jens J.</creator><creator>Fölsch, Ulrich R.</creator><creator>Creutzfeldt, Werner</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>19941201</creationdate><title>Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans</title><author>Schmidt, Wolfgang E. ; Schenk, Stefan ; Nustede, Rainer ; Holst, Jens J. ; Fölsch, Ulrich R. ; Creutzfeldt, Werner</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-94aefa510acfddc1e9e9bc66b924fc810dbfc264ca539d9c385be7c0f44662053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Cholecystokinin - pharmacology</topic><topic>Cholecystokinin - physiology</topic><topic>Eating</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastric Acid - metabolism</topic><topic>Gastric Mucosa - drug effects</topic><topic>Gastric Mucosa - metabolism</topic><topic>Gastrins - metabolism</topic><topic>Gastrins - pharmacology</topic><topic>Gastrointestinal hormones</topic><topic>Humans</topic><topic>Male</topic><topic>Proglumide - analogs & derivatives</topic><topic>Proglumide - pharmacology</topic><topic>Radioimmunoassay</topic><topic>Receptors, Cholecystokinin - antagonists & inhibitors</topic><topic>Somatostatin - blood</topic><topic>Stomach - drug effects</topic><topic>Vertebrates: digestive system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmidt, Wolfgang E.</creatorcontrib><creatorcontrib>Schenk, Stefan</creatorcontrib><creatorcontrib>Nustede, Rainer</creatorcontrib><creatorcontrib>Holst, Jens J.</creatorcontrib><creatorcontrib>Fölsch, Ulrich R.</creatorcontrib><creatorcontrib>Creutzfeldt, Werner</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>Schmidt, Wolfgang E.</au><au>Schenk, Stefan</au><au>Nustede, Rainer</au><au>Holst, Jens J.</au><au>Fölsch, Ulrich R.</au><au>Creutzfeldt, Werner</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans</atitle><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle><addtitle>Gastroenterology</addtitle><date>1994-12-01</date><risdate>1994</risdate><volume>107</volume><issue>6</issue><spage>1610</spage><epage>1620</epage><pages>1610-1620</pages><issn>0016-5085</issn><eissn>1528-0012</eissn><coden>GASTAB</coden><abstract>Background/Aims: The role of cholecystokinin (CCK) in the regulation of gastric acid secretion is still controversial. This study examined the effect of the CCK-A receptor antagonist loxiglumide (lox) on gastrin- or CCK-induced gastric acid secretion and meal-stimulated plasma gastrin levels in a placebo-controlled study. Methods: Acid output was studied in eight subjects who received intravenously gastrin-17 (15, 30, and 60 pmol·kg−1·h−1); gastrin-17 plus lox; cholecystokinin octapeptide (CCK-8) (15, 30, and 60 pmol·kg−1·h−1); CCK-8 plus lox; or gastrin plus CCK-8. Sham feeding-induced acid output and meal-stimulated gastrin secretion were studied during lox infusion. Results: Gastrin-17 dose-dependently stimulated acid output to near-maximal levels. CCK-8 (15 pmol· kg−1·h−1) increased acid secretion 2.5-fold over basal; higher infusion rates had less or no effect. When combined with lox, CCK-8 produced a near-maximal acid response (6-fold over basal). CCK-8 together with gastrin-17 inhibited gastrin-induced acid output by 67%. Meal-stimulated plasma gastrin concentrations were elevated 3.2-fold, whereas sham feeding-induced acid secretion was not modified by lox. Conclusions: Blockade of CCK-A receptors converts CCK-8 into a potent acid secretagogue and augments postprandial gastrin secretion. A CCK-mediated stimulation of paracrine somatostatin secretion from antrat and fundic D cells represents a candidate mechanism for the inhibition of the parietal and gastrin cell in humans.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>7958670</pmid><doi>10.1016/0016-5085(94)90799-4</doi><tpages>11</tpages></addata></record> |
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| ispartof | Gastroenterology (New York, N.Y. 1943), 1994-12, Vol.107 (6), p.1610-1620 |
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| subjects | Adult Biological and medical sciences Cholecystokinin - pharmacology Cholecystokinin - physiology Eating Fundamental and applied biological sciences. Psychology Gastric Acid - metabolism Gastric Mucosa - drug effects Gastric Mucosa - metabolism Gastrins - metabolism Gastrins - pharmacology Gastrointestinal hormones Humans Male Proglumide - analogs & derivatives Proglumide - pharmacology Radioimmunoassay Receptors, Cholecystokinin - antagonists & inhibitors Somatostatin - blood Stomach - drug effects Vertebrates: digestive system |
| title | Cholecystokinin is a negative regulator of gastric acid secretion and postprandial release of gastrin in humans |
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