Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans

Ngai Moh Law, Adil Eddie Bharucha, Anita S. Undale, Alan R. Zinsmeister

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

The cholinesterase inhibitor neostigmine indirectly stimulates muscarinic M1/M2/M3 receptors, thereby reducing colonic distension in acute colonic pseudo-obstruction. We investigated the dose-response profile for the colonic sensorimotor effects of neostigmine and bethanechol, a direct muscarinic M2/M3 agonist in humans. A barostat-manometric assembly recorded phasic pressures, tone, and pressure-volume relationships (compliance) in the descending colon and rectum of 30 healthy subjects who received intravenous neostigmine (0.25, 0.75, or 1.5 mg; n = 15) or subcutaneous bethanechol (2.5, 5, or 10 mg; n = 15). Sensation to luminal distension was also assessed. Thereafter, the effects of neostigmine and bethanechol on colonic transit (geometric center) were compared with those of saline by scintigraphy in 21 subjects. Both drugs increased colonic phasic pressure activity, reduced rectal compliance, and enhanced urgency during rectal distension. Neostigmine also reduced colonic and rectal balloon volumes, reflecting increased tone by an average of 12% and 25% for the highest dose, respectively. Only neostigmine reduced colonic compliance, accelerated colonic transit [mean geometric center at 90 min 2.5 vs. 1.0 (placebo)], and increased pain perception during colonic distension. We conclude that neostigmine has more prominent colonic motor and sensory effects than bethanechol. Moreover, neostigmine induces coordinated colonic propulsion, perhaps by stimulating muscarinic M1 receptors in the myenteric plexus.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number5 44-5
StatePublished - 2001

Fingerprint

Neostigmine
Cholinergic Agents
Motor Activity
Bethanechol
Compliance
Pressure
Colonic Pseudo-Obstruction
Muscarinic M1 Receptors
Descending Colon
Myenteric Plexus
Pain Perception
Cholinesterase Inhibitors
Rectum
Radionuclide Imaging
Healthy Volunteers
Placebos

Keywords

  • Bethanechol
  • Colonic tone
  • Compliance
  • Neostigmine
  • Sensation

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans. / Law, Ngai Moh; Bharucha, Adil Eddie; Undale, Anita S.; Zinsmeister, Alan R.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 281, No. 5 44-5, 2001.

Research output: Contribution to journalArticle

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