Digestive Diseases and Sciences

, Volume 41, Issue 10, pp 2006–2015 | Cite as

M1-muscarinic mechanisms regulate interdigestive cycling of motor and secretory activity in human upper gut

  • Daniel K. Nelson
  • Oreste Pieramico
  • Gudrun Dahmen
  • J. Enrique Dominguez-Muñoz
  • Peter Malfertheiner
  • Guido Adler
Motility, Nerve-Gut Interactions, Hormones, And Receptors

Abstract

We determined the influence of M1-muscarinic pathways in modulating temporal cycling of motor and secretory activity in the fasting upper gut. Eight healthy subjects were studied on two separate days, following a double-blind, randomized protocol. Antroduodenal motility (migrating motor complex, MMC), pancreatic exocrine secretion (amylase, lipase, trypsin, chymotrypsin), and plasma levels of associated hormones [motilin, pancreatic polypeptide (PP)] were monitored for two consecutive cycles during background infusion of placebo or telenzepine, a selective M1-muscarinic receptor antagonist. On placebo days, pancreatic enzymes and hormones cycled in synchrony with motor activity, as expected. During M1 blockade, duodenal output of each enzyme was decreased by 85–90% in phase I and by >90% in phase III. Similarly, plasma concentrations of hormones were decreased during all phases and cycling was absent. Despite the loss of these putative influences, intestinal motility continued to cycle, albeit in an altered fashion. Intermittent phase II activity was replaced by phase I quiescence, while phase III-like fronts were diminished (contraction frequency, amplitude, propagation velocity reduced 30–60%, duration not altered) but recurred at expected intervals (cycle length 105±14 min vs 109±12 in placebo). Gastric motor activity was virtually abolished. These data suggest or extend several working hypotheses: (1) Motilin is released and/or acts via cholinergic (M1-muscarinic) pathways to initiate antral, but not duodenal, phase III activity. (2) M1 receptors mediate all components of the gastric MMC and phase II activity throughout the gut, but intestinal phase III activity arises via alternate pathways. (3) M1-muscarinic mechanisms regulate interdigestive cycling of pancreatic enzymes and PP. (4) Secretions from the endocrine/exocrine pancreas are not primary mediators of intestinal motility.

Key words

interdigestive cycling motility pancreatic exocrine secretion enzymes motilin pancreatic polypeptide hormones M1-muscarinic receptors cholinergic 

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Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Daniel K. Nelson
    • 1
    • 2
    • 3
    • 4
  • Oreste Pieramico
    • 1
    • 2
    • 3
    • 4
  • Gudrun Dahmen
    • 1
    • 2
    • 3
    • 4
  • J. Enrique Dominguez-Muñoz
    • 1
    • 2
    • 3
    • 4
  • Peter Malfertheiner
    • 1
    • 2
    • 3
    • 4
  • Guido Adler
    • 1
    • 2
    • 3
    • 4
  1. 1.From the University of UlmUlmGermany
  2. 2.Isaac Gordon Center for Digestive Diseases and NutritionThe Genesee Hospital, University of RochesterRochester
  3. 3.General HospitalMeranItaly
  4. 4.University of MagdeburgMagdeburgGermany

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