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Gastrointestinal motor and secretory responses to cholinergic stimulation in humans. Differential modulation by muscarinic and cholecystokinin receptor blockade.
Eur J Clin Invest. 1995 Feb; 25(2):113-22.EJ

Abstract

The present study investigated how a cholinergic agonist modifies interdigestive motility and secretion of the upper gastrointestinal tract and how muscarinic and cholecystokinin receptor blockade interfere with this direct cholinergic stimulation. In eight healthy volunteers, gastrointestinal motor and secretory responses to bethanechol (12.5, 25, and 50 micrograms kg-1 h-1) with and without a background of atropine (5 micrograms kg-1 h-1) or loxiglumide (10 mg kg-1 h-1) were studied. Stepdoses of bethanechol caused a parallel stimulation of antroduodenal motility and gastropancreatic secretion (P < 0.01) without inducing a fed pattern. However, duration of phase I was shortened (P < 0.05). Only high doses of bethanechol enhanced gastrin (P < 0.05), cholecystokinin (P < 0.05), and pancreatic polypeptide (P < 0.01) release. Atropine completely antagonized motor and secretory responses to cholinergic stimulation. Loxiglumide left cholinergically stimulated motility and pancreatic enzyme secretion unaltered. With co-infusion of bethanechol and loxiglumide, PP release dropped by 63% (P < 0.01); gastric acid output, gastrin and CCK release increased by 56%, 16%, and 25%, respectively (P < 0.05). We conclude that stimulation by a cholinergic agonist preserves the interdigestive pattern. Low dose muscarinic receptor blockade abolishes cholinergic stimulation over the full dose range. Inhibition of somatostatin release would explain stimulation of gastrin release and gastric acid secretion with co-infusion of bethanechol and loxiglumide. Endogenous CCK appears to interact with direct cholinergic stimulation at the pancreatic PP cell and the gastric D-cell but not at pancreatic acinar and antroduodenal smooth muscle cells.

Authors+Show Affiliations

Department of Gastroenterology, University Hospital of Marburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7737260

Citation

Katschinski, M, et al. "Gastrointestinal Motor and Secretory Responses to Cholinergic Stimulation in Humans. Differential Modulation By Muscarinic and Cholecystokinin Receptor Blockade." European Journal of Clinical Investigation, vol. 25, no. 2, 1995, pp. 113-22.
Katschinski M, Steinicke C, Reinshagen M, et al. Gastrointestinal motor and secretory responses to cholinergic stimulation in humans. Differential modulation by muscarinic and cholecystokinin receptor blockade. Eur J Clin Invest. 1995;25(2):113-22.
Katschinski, M., Steinicke, C., Reinshagen, M., Dahmen, G., Beglinger, C., Arnold, R., & Adler, G. (1995). Gastrointestinal motor and secretory responses to cholinergic stimulation in humans. Differential modulation by muscarinic and cholecystokinin receptor blockade. European Journal of Clinical Investigation, 25(2), 113-22.
Katschinski M, et al. Gastrointestinal Motor and Secretory Responses to Cholinergic Stimulation in Humans. Differential Modulation By Muscarinic and Cholecystokinin Receptor Blockade. Eur J Clin Invest. 1995;25(2):113-22. PubMed PMID: 7737260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gastrointestinal motor and secretory responses to cholinergic stimulation in humans. Differential modulation by muscarinic and cholecystokinin receptor blockade. AU - Katschinski,M, AU - Steinicke,C, AU - Reinshagen,M, AU - Dahmen,G, AU - Beglinger,C, AU - Arnold,R, AU - Adler,G, PY - 1995/2/1/pubmed PY - 1995/2/1/medline PY - 1995/2/1/entrez SP - 113 EP - 22 JF - European journal of clinical investigation JO - Eur J Clin Invest VL - 25 IS - 2 N2 - The present study investigated how a cholinergic agonist modifies interdigestive motility and secretion of the upper gastrointestinal tract and how muscarinic and cholecystokinin receptor blockade interfere with this direct cholinergic stimulation. In eight healthy volunteers, gastrointestinal motor and secretory responses to bethanechol (12.5, 25, and 50 micrograms kg-1 h-1) with and without a background of atropine (5 micrograms kg-1 h-1) or loxiglumide (10 mg kg-1 h-1) were studied. Stepdoses of bethanechol caused a parallel stimulation of antroduodenal motility and gastropancreatic secretion (P < 0.01) without inducing a fed pattern. However, duration of phase I was shortened (P < 0.05). Only high doses of bethanechol enhanced gastrin (P < 0.05), cholecystokinin (P < 0.05), and pancreatic polypeptide (P < 0.01) release. Atropine completely antagonized motor and secretory responses to cholinergic stimulation. Loxiglumide left cholinergically stimulated motility and pancreatic enzyme secretion unaltered. With co-infusion of bethanechol and loxiglumide, PP release dropped by 63% (P < 0.01); gastric acid output, gastrin and CCK release increased by 56%, 16%, and 25%, respectively (P < 0.05). We conclude that stimulation by a cholinergic agonist preserves the interdigestive pattern. Low dose muscarinic receptor blockade abolishes cholinergic stimulation over the full dose range. Inhibition of somatostatin release would explain stimulation of gastrin release and gastric acid secretion with co-infusion of bethanechol and loxiglumide. Endogenous CCK appears to interact with direct cholinergic stimulation at the pancreatic PP cell and the gastric D-cell but not at pancreatic acinar and antroduodenal smooth muscle cells. SN - 0014-2972 UR - https://www.unboundmedicine.com/medline/citation/7737260/Gastrointestinal_motor_and_secretory_responses_to_cholinergic_stimulation_in_humans__Differential_modulation_by_muscarinic_and_cholecystokinin_receptor_blockade_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0014-2972&amp;date=1995&amp;volume=25&amp;issue=2&amp;spage=113 DB - PRIME DP - Unbound Medicine ER -