NEUROENDOCRINE CONTROL OF SMALL INTESTINAL MOTILITY

Project: Research project

Description

Both the intrinsic nerves and gut neuropeptides are known to
regulate muscle contraction and relaxation in the small intestine.
However, how nerves and peptides act together to regulate
neuromuscular transmission is not well understood. The aim of
this proposal is to define the neural and endocrine controls which
regulate neuromuscular transmission in the rodent small intestine. Segments of duodenum and ileum are mounted in baths of Krebs
solution gassed with 95% 0/2 - 5% Co/2 at 37/0 and stretched to
optimal lengths. Each segment undergoes electrical field
stimulation and the fluid bathing each segment is removed and
assayed for vasoactive intestinal polypeptide (VIP), motilin,
cholecystokinin, (CCK) and substance P. Atropine is used to study
the effect of muscarinic blockade on neuropeptide release.
Current amplitude during field stimulation is varied to selectively
activate cholinergic excitatory nerves, non-cholinergic excitatory
nerves, and non-cholinergic inhibitory nerves. A separate study examines the influence of neuropeptides and
peptide antagonists or antisera on neuromuscular transmission.
Circular and longitudinal muscle strips are stretched to optimal
lengths and tensions are measured continuously. Resting and
field-stimulated tensions are monitored as tissues are superfused
with: 1) VIP, CCK, substance P, motilin, or met- and leu-
enkephalin; 2) antisera to VIP, CCK, motilin, and substance P; 3)
naloxone or proglumide. Current amplitude during field
stimulation is varied to determine the effects of these agents on
cholinergic excitatory nerves, non-cholinergic excitatory nerves,
and non-cholinergic inhibitory nerves. Since preliminary
observations suggest that current direction can preferentially
activate excitatory or inhibitory nerves, a separate study
examines the influence of directed electrical field stimulation
applied at various current amplitudes on neuromuscular
transmission. A final study examines enteric neuromuscular transmission in
experimental diabetes mellitus. Neuropeptides release is studied
in streptozotocin-treated rats, controls, and insulin-treated
diabetic rats, while separate studies examine the effects of VIP,
CCK, and motilin on enteric neuromuscular transmission in these
animals. These experiments will help clarify the mechanism of
neuropeptidergic transmission in the enteric nervous system.
Ultimately, this study will help to better understand the
pathophysiology of motor abnormalities such as intestinal
pseudoobstruction, paralytic ileus, and diabetic enteropathy.
StatusFinished
Effective start/end date7/20/878/31/93

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Motilin
Gastrointestinal Motility
Vasoactive Intestinal Peptide
Cholecystokinin
Neuropeptides
Substance P
Cholinergic Agents
Small Intestine
Immune Sera
Proglumide
Intestinal Pseudo-Obstruction
Enteric Nervous System
Leucine Enkephalin
Methionine Enkephalin
Muscle Relaxation
Streptozocin
Naloxone
Muscle Contraction
Baths
Atropine

ASJC

  • Medicine(all)